Automatic determination of Greulich and Pyle bone age in healthy Dutch children

Background: Bone age (BA) assessment is a routine procedure in paediatric radiology, for which the Greulich and Pyle (GP) atlas is mostly used. There is rater variability, but the advent of automatic BA determination eliminates this. Objective: To validate the BoneXpert method for automatic determination of skeletal maturity of healthy children against manual GP BA ratings. Materials and methods: Two observers determined GP BA with knowledge of the chronological age (CA). A total of 226 boys with a BA of 3-17 years and 179 girls with a BA of 3-15 years were included in the study. BoneXpert's estimate of GP BA was calibrated to agree on average with the manual ratings based on several studies, including the present study. Results: Seven subjects showed a deviation between manual and automatic BA in excess of 1.9 years. They were re-rated blindly by two raters. After correcting these seven ratings, the root mean square error between manual and automatic rating in the 405 subjects was 0.71 years (range 0.66-0.76 years, 95% CI). BoneXpert's GP BA is on average 0.28 and 0.20 years behind the CA for boys and girls, respectively. Conclusion: BoneXpert is a robust method for automatic determination of BA

Genomic Instability, Defective Spermatogenesis, Immunodeficiency, and Cancer in a Mouse Model of the RIDDLE Syndrome

Eukaryotic cells have evolved to use complex pathways for DNA damage signaling and repair to maintain genomic integrity. RNF168 is a novel E3 ligase that functions downstream of ATM,γ-H2A.X, MDC1, and RNF8. It has been shown to ubiquitylate histone H2A and to facilitate the recruitment of other DNA damage response proteins, including 53BP1, to sites of DNA break. In addition, RNF168 mutations have been causally linked to the human RIDDLE syndrome. In this study, we report that Rnf168−/− mice are immunodeficient and exhibit increased radiosensitivity. Rnf168−/− males suffer from impaired spermatogenesis in an age-dependent manner. Interestingly, in contrast to H2a.x−/−, Mdc1−/−, and Rnf8−/− cells, transient recruitment of 53bp1 to DNA double-strand breaks was abolished in Rnf168−/− cells. Remarkably, similar to 53bp1 inactivation, but different from H2a.x deficiency, inactivation of Rnf168 impairs long-range V(D)J recombination in thymocytes and results in long insertions at the class-switch junctions of B-cells. Loss of Rnf168 increases genomic instability and synergizes with p53 inactivation in promoting tumorigenesis. Our data reveal the important physiological functions of Rnf168 and support its role in both γ-H2a.x-Mdc1-Rnf8-dependent and -independent signaling pathways of DNA double-strand breaks. These results highlight a central role for RNF168 in the hierarchical network of DNA break signaling that maintains genomic integrity and suppresses cancer development in mammals

Epiphyseal union sequencing: aiding in the recognition and sorting of commingled remains

The presence of accessory osseous material within a seemingly single individual assemblage has the potential to result in misidentification of the remains. Detection of nonrelated material relies on the anthropologist being able to recognize incongruities among the elements. Inconsistencies in developmental status provide evidence to suggest that commingling may have occurred. Analyzing the sequence in which the various epiphyses unite can help to identify outlying elements that do not match the predicted developmental pattern of the remaining skeleton, thus indicating that the element may not belong to that individual. This paper considers the sequence in which 21 various epiphyses of the body unite to serve as a reference for identifying incongruent fusing patterns within a commingled assemblage. Two hundred and fifty-eight male individuals of Bosniak (Bosnian Muslim) descent between the ages of 14 and 30 years were included for analysis. Sequence order was determined for both ‘‘beginning’’ and ‘‘complete’’ union by comparing the fusing status of each epiphysis with each of the other 21 epiphyses. Considering both sequence patterns provides a wider spectrum of evidence from which to recognize incongruities than either sequence pattern could provide in isolation. Variations to the majority sequence pattern were also included to ensure that skeletons displaying less popular but acceptable sequence patterns would not be mistakenly considered as two individuals when using this research as a reference. Although substantial variation in the order in which epiphyses initiate and complete union was discovered within the sample, most epiphyseal relationships did not display any variable patterns. These ‘‘unvaried’’ relationships will be most useful in recognizing the presence of incongruent material if the pattern within an assemblage does not conform to the pattern documented in this study. Figures demonstrating the two sequence patterns are provided for easy application in the field

A method to establish the relationship between chronological age and stage of union from radiographic assessment of epiphyseal fusion at the knee: an Irish population study

Characteristic changes during epiphyseal union provide a skeletal age, which when compared with age-based standards provides an estimation of chronological age. Currently there are no data on epiphyseal union for the purposes of age estimation specific to an Irish population. This cross-sectional study aims to investigate the relationship between stage of epiphyseal union at the knee joint and chronological age in a modern Irish population. A novel radiographic method that sub-divides the continuum of development into five specific stages of union is presented. Anteroposterior and lateral knee radiographs of 148 males and 86 females, aged 9–19 years, were examined. Fusion was scored as Stage 0, non-union; Stage 1, beginning union; Stage 2, active union; Stage 3, recent union; or Stage 4, complete union. Stage of epiphyseal union is correlated with chronological age in both males and females. Mean age gradually increases with each stage of union and also varies between male and female subjects. A statistically significant difference in mean age was recorded between stages when compared to the previous stage, for the three epiphyses. Irish children are comparable to those from previously published studies with epiphyseal union in females occurring earlier than males. A significant difference was noted between the mean age of union for males and females for each of Stages 1 and 2 for the femur and Stages 0, 1, 2 and 3 for the tibia and the fibula. The results also suggest that the stages of union occur at earlier ages in this Irish population. Implementation of standardized methodology is necessary to investigate if this is due to a secular or population variation in maturation or to a methodology which clearly identifies five stages of union

Role of growth hormone in enchondroplasia and chondral osteogenesis: evaluation by X-ray of the hand

BACKGROUND: The process of growth and maturation of long (radius and ulna) and short (metacarpals and phalanges) bones of the hand (enchondroplasia) differs from that of the carpal cuboid bones (chondral osteogenesis). This study aimed to assess the impact of growth hormone (GH) on these two processes of bone maturation. METHODS: Subjects of the study were 95 prepubertal children: 30 children with GH deficiency and 65 children with idiopathic short stature, aged 7.4 +/- 1.9 y (mean +/- SD) (trial registration number 98-0198-033). Bone maturation was assessed by the Greulich and Pyle method from X-rays obtained at the start and at 1 and 2 y of GH treatment, separately for carpals, long bones, and short bones, and was expressed as years of delay relative to chronological age. RESULTS: At GH start, the delay in bone maturation in the GH-deficient group was significantly greater for carpals (3.6 +/- 1.3 y) than for long (3.0 +/- 1.3 y) and short (1.7 +/- 1.1 y) bones. The delay was nonsignificantly greater for carpal bones in GH-deficient subjects than in subjects with idiopathic short stature (3.6 +/- 1.3 vs. 3.1 +/- 1.1 y, respectively) and was normalized after 2 y of GH treatment. CONCLUSION: The dominant effect of GH was on chondral osteogenesis, with milder effect on enchondroplasia. A distinct delay in carpal and long-bone maturation, which normalizes during 2 y of GH treatment, was typical in GH-deficient children. Therefore, separate carpal bone assessment in bone age reading is needed.</p