Hereditary hypophosphatemia in Norway: A retrospective population-based study of genotypes, phenotypes, and treatment complications

Objective: Hereditary hypophosphatemias (HH) are rare monogenic conditions characterized by decreased renal tubular phosphate reabsorption. The aim of this study was to explore the prevalence, genotypes, phenotypic spectrum, treatment response, and complications of treatment in the Norwegian population of children with HH. Design: Retrospective national cohort study. Methods: Sanger sequencing and multiplex ligand-dependent probe amplification analysis of PHEX and Sanger sequencing of FGF23, DMP1, ENPP1KL, and FAM20C were performed to assess genotype in patients with HH with or without rickets in all pediatric hospital departments across Norway. Patients with hypercalcuria were screened for SLC34A3 mutations. In one family, exome sequencing was performed. Information from the patients' medical records was collected for the evaluation of phenotype. Results: Twety-eight patients with HH (18 females and ten males) from 19 different families were identified. X-linked dominant hypophosphatemic rickets (XLHR) was confirmed in 21 children from 13 families. The total number of inhabitants in Norway aged 18 or below by 1st January 2010 was 1 109 156, giving an XLHR prevalence of ∼1 in 60 000 Norwegian children. FAM20C mutations were found in two brothers and SLC34A3 mutations in one patient. In XLHR, growth was compromised in spite of treatment with oral phosphate and active vitamin D compounds, with males tending to be more affected than females. Nephrocalcinosis tended to be slightly more common in patients starting treatment before 1 year of age, and was associated with higher average treatment doses of phosphate. However, none of these differences reached statistical significance. Conclusions: We present the first national cohort of HH in children. The prevalence of XLHR seems to be lower in Norwegian children than reported earlier.publishedVersio

Psychological health in preschool children with underweight, overweight or obesity: a regional cohort study

Objective To examine if underweight (UW), overweight (OW) or obesity (OB), or body mass index (BMI) expressed as its SD score (BMI SDS), were associated with psychological difficulties in preschool children. Design Regional cohort study. Setting Oppland County, Norway. Methods At the routine school entry health assessment at 5–6 years of age, parents were invited to participate by local public health nurses. The parents completed questionnaires on sociodemographic, health and lifestyle factors of the child and the family, and on the child’s neurocognitive development. They assessed psychological health with the Strengths and Difficulties Questionnaire (SDQ). Public health nurses measured weight and height on all eligible children and reported age, sex, height and weight anonymously for the children who declined to participate. Participants We obtained information on 1088 of 1895 (57%) eligible children. The proportion of UW, OW and OB was slightly higher among the children who declined. Main outcome measures SDQ subscale and Total Difficulties Scores. Results The mean SDQ scores and proportion of scores ≥the 90th percentile had a curvilinear pattern from UW through normal weight (NW), OW and OB with NW as nadir, but the pattern was only significant for the mean Emotional problems, Peer problems and Total SDQ Scales, and for the Total SDQ Score ≥the 90th percentile (TDS90). After adjusting for relevant social, developmental, health and behavioural characteristics, TDS90 was only significantly associated with UW in multiple logistic regression analyses, and only with the lowest quartile of BMI SDS in a linear spline regression analysis. Conclusions The study suggests that UW and low BMI, but not OW, OB or higher BMI, are independent risk factors for having psychological symptoms in preschool children.publishedVersio

Hormone references for ultrasound breast staging and endocrine profiling to detect female onset of puberty

Context - Application of ultrasound (US) to evaluate attainment and morphology of glandular tissue provides a new rationale for evaluating onset and progression of female puberty, but currently no hormone references complement this method. Furthermore, previous studies have not explored the predictive value of endocrine profiling to determine female puberty onset. Objective - To integrate US breast staging with hypothalamic-pituitary-gonadal hormone references and test the predictive value of an endocrine profile to determine thelarche. Design Setting and Participants - Cross-sectional sample of 601 healthy Norwegian girls, ages 6 to 16 years. Main Outcome Measures - Clinical and ultrasound breast evaluations were performed for all included girls. Blood samples were analyzed by immunoassay and ultrasensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) to quantify estradiol (E2) and estrone (E1) from the subpicomolar range. Results - References for E2, E1, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin were constructed in relation to chronological age, Tanner stages, and US breast stages. An endocrine profile index score derived from principal component analysis of these analytes was a better marker of puberty onset than age or any individual hormone, with receiver-operating characteristic area under the curve 0.91 (P < 0.001). Ultrasound detection of nonpalpable glandular tissue in 14 out of 264 (5.3%) girls with clinically prepubertal presentation was associated with significantly higher median serum levels of E2 (12.5 vs 4.9 pmol/L; P < 0.05) and a distinct endocrine profile (arbitrary units; P < 0.001). Conclusions - We provide the first hormone references for use with US breast staging and demonstrate the application of endocrine profiling to improve detection of female puberty onset

Testicular ultrasound to stratify hormone references in a cross-sectional Norwegian study of male puberty

Context: Testicular growth represents the best clinical variable to evaluate male puberty, but current pediatric hormone references are based on chronological age and subjective assessments of discrete puberty development stages. Determination of testicular volume (TV) by ultrasound provides a novel approach to assess puberty progression and stratify hormone reference intervals. Objective: The objective of this article is to establish references for serum testosterone and key hormones of the male pituitary-gonadal signaling pathway in relation to TV determined by ultrasound. Design, Setting, and Participants: Blood samples from 414 healthy Norwegian boys between ages 6 and 16 years were included from the cross-sectional “Bergen Growth Study 2.” Participants underwent testicular ultrasound and clinical assessments, and serum samples were analyzed by liquid chromatography tandem–mass spectrometry and immunoassays. Main Outcome Measures: We present references for circulating levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin in relation to TV, chronological age, and Tanner pubic hair stages. Results: In pubertal boys, TV accounted for more variance in serum testosterone levels than chronological age (Spearman r = 0.753, P < .001 vs r = 0.692, P < .001, respectively). Continuous centile references demonstrate the association between TV and hormone levels during puberty. Hormone reference intervals were stratified by TV during the pubertal transition. Conclusions: Objective ultrasound assessments of TV and stratification of hormone references increase the diagnostic value of traditional references based on chronological age or subjective staging of male puberty.acceptedVersio

History of climate modeling

The history of climate modeling begins with conceptual models, followed in the 19th century by mathematical models of energy balance and radiative transfer, as well as simple analog models. Since the 1950s, the principal tools of climate science have been computer simulation models of the global general circulation. From the 1990s to the present, a trend toward increasingly comprehensive coupled models of the entire climate system has dominated the field. Climate model evaluation and intercomparison is changing modeling into a more standardized, modular process, presenting the potential for unifying research and operational aspects of climate science. WIREs Clim Change 2011 2 128–139 DOI: 10.1002/wcc.95 For further resources related to this article, please visit the WIREs websitePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79438/1/95_ftp.pd

A gene trap transposon eliminates haematopoietic expression of zebrafish Gfi1aa, but does not interfere with haematopoiesis

A transposon-mediated gene trap screen identified the zebrafish line qmc551 that expresses a GFP reporter in primitive erythrocytes and also in haemogenic endothelial cells, which give rise to haematopoietic stem and progenitor cells (HSPCs) that seed sites of larval and adult haematopoiesis. The transposon that mediates this GFP expression is located in intron 1 of the gfi1aa gene, one of three zebrafish paralogs that encode transcriptional repressors homologous to mammalian Gfi1 and Gfi1b proteins. In qmc551 transgenics, GFP expression is under the control of the endogenous gfi1aa promoter, recapitulates early gfi1aa expression and allows live observation of gfi1aa promoter activity. While the transposon integration interferes with the expression of gfi1aa mRNA in haematopoietic cells, homozygous qmc551 fish are viable and fertile, and display normal primitive and definitive haematopoiesis. Retained expression of Gfi1b in primitive erythrocytes and upregulation of Gfi1ab at the onset of definitive haematopoiesis in homozygous qmc551 carriers, are sufficient to allow normal haematopoiesis. This finding contradicts previously published morpholino data that suggested an essential role for zebrafish Gfi1aa in primitive erythropoiesi

Interrelationships between anthropometric variables and overweight in childhood and adolescence

Objectives To answer the questions: how does body mass index (BMI) correlate to five overweight related anthropometric variables during different ages in childhood, and which anthropometric variables contribute most to variation in BMI during childhood? Methods Data on BMI, height (H), sitting height (SH), waist circumference (WC), waist to height ratio (WHtR), waist to sitting height ratio (WSHtR), subscapular skinfold (SSF), and triceps skinfold (TSF), from 4,576 Norwegian children 4.00–15.99 years of age, were transformed to standard deviation scores (SDS) and studied using correlation and multiple regression analyses. Results The correlations between BMI SDS and the standardized anthropometric variables were in general strong and positive. For all variables, the correlations were weakest in the youngest age group and highest between 7 and 12 years. WC SDS and WHtR SDS were most strongly correlated with BMI SDS through all ages and in both sexes. A model with seven anthropometric variables adjusted for age and sex explained 81.4% of the variation in BMI SDS. When adjusted for all other variables, WC SDS contributed most to the variation in BMI SDS (b = 0.467, CI [0.372, 0.562]). Age group, but not sex, contributed significantly to variation in BMI SDS. Conclusion The interrelationships between BMI SDS and five standardized overweight related anthropometric variables were dependent on age, being weakest in the youngest age group. Independent of sex and age, WC SDS was in this study superior to other anthropometric variables in contributing to variation in BMI SDS during childhood. Am. J. Hum. Biol. 26:502–510, 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc