A probability model for estimating age in young individuals relative to key legal thresholds: 15, 18 or 21-year.

Age estimations are relevant for pre-trial detention, sentencing in criminal cases and as part of the evaluation in asylum processes to protect the rights and privileges of minors. No current method can determine an exact chronological age due to individual variations in biological development. This study seeks to develop a validated statistical model for estimating an age relative to key legal thresholds (15, 18, and 21 years) based on a skeletal (CT-clavicle, radiography-hand/wrist or MR-knee) and tooth (radiography-third molar) developmental stages. The whole model is based on 34 scientific studies, divided into examinations of the hand/wrist (15 studies), clavicle (5 studies), distal femur (4 studies), and third molars (10 studies). In total, data from approximately 27,000 individuals have been incorporated and the model has subsequently been validated with data from 5,000 individuals. The core framework of the model is built upon transition analysis and is further developed by a combination of a type of parametric bootstrapping and Bayesian theory. Validation of the model includes testing the models on independent datasets of individuals with known ages and shows a high precision with separate populations aligning closely with the model's predictions. The practical use of the complex statistical model requires a user-friendly tool to provide probabilities together with the margin of error. The assessment based on the model forms the medical component for the overall evaluation of an individual's age.

A probability model for assessing age relative to the 18-year old threshold based on magnetic resonance imaging of the knee combined with radiography of third molars in the lower jaw.

OBJECTIVE: This study aims to generate a statistical model based on magnetic resonance imaging of the knee and radiography of third molars in the lower jaw, for assessing age relative to the 18-year old threshold. METHODS: In total, 58 studies correlating knee or tooth development to age were assessed, 5 studies for knee and 7 studies for tooth were included in the statistical model. The relation between the development of the anatomical site, based on a binary system, and age were estimated using logistic regression. Separate meta-populations for knee and tooth were generated from the individual based data for men and women. A weighted estimate of probabilities was made by combining the probability densities for knee and tooth. Margin of errors for males and females in different age groups and knee and tooth maturity were calculated within the larger framework of transition analysis using a logit model as a base. Evidentiary values for combinations of knee and tooth maturity were evaluated with likelihood ratios. RESULTS: For males, the sensitivity for the method was calculated to 0.78 (probability of correctly classifying adults), the specificity 0.90 (probability of correctly classifying minors), the negative predictive value 0.80 (proportion identified minors are minors) and the positive predictive value 0.89 (proportion identified adults are adults) indicating a model better at identifying minors than adults. The point at which half the female population has reached closed knee lies before the 18-year threshold, adding the knee as an indicator lowers specificity and increases sensitivity. The sensitivity when using tooth as an indicator for females is 0.24 and specificity 0.97, signifying few minors misclassified as adults but also a low probability of identifying adults. The negative predictive value for women when using tooth as the sole indicator is 0.56 and positive predictive value 0.88. Probabilities were calculated for males and females assuming a uniform age distribution between 15 and 21years. The calculated margin of error of minors classified as adults in a population between 15 and 21 years with the model was 11% for males and 12% for females. Further, the evidentiary value as well as margin of error vary for different combinations of knee and tooth maturity. CONCLUSION: The statistical model based on the combination of MRI knee and radiography of mandibular third molars is a valid method to assess age relative to the 18-year old threshold when applied on males and of limited value in females.

Cell type boundaries organize plant development.

In plants the dorsoventral boundary of leaves defines an axis of symmetry through the centre of the organ separating the top (dorsal) and bottom (ventral) tissues. Although the positioning of this boundary is critical for leaf morphogenesis, how the boundary is established and how it influences development remains unclear. Using live-imaging and perturbation experiments we show that leaf orientation, morphology and position are pre-patterned by HD-ZIPIII and KAN gene expression in the shoot, leading to a model in which dorsoventral genes coordinate to regulate plant development by localizing auxin response between their expression domains. However we also find that auxin levels feedback on dorsoventral patterning by spatially organizing HD-ZIPIII and KAN expression in the shoot periphery. By demonstrating that the regulation of these genes by auxin also governs their response to wounds, our results also provide a parsimonious explanation for the influence of wounds on leaf dorsoventrality.

A Model Analysis of Mechanisms for Radial Microtubular Patterns at Root Hair Initiation Sites.

Plant cells have two main modes of growth generating anisotropic structures. Diffuse growth where whole cell walls extend in specific directions, guided by anisotropically positioned cellulose fibers, and tip growth, with inhomogeneous addition of new cell wall material at the tip of the structure. Cells are known to regulate these processes via molecular signals and the cytoskeleton. Mechanical stress has been proposed to provide an input to the positioning of the cellulose fibers via cortical microtubules in diffuse growth. In particular, a stress feedback model predicts a circumferential pattern of fibers surrounding apical tissues and growing primordia, guided by the anisotropic curvature in such tissues. In contrast, during the initiation of tip growing root hairs, a star-like radial pattern has recently been observed. Here, we use detailed finite element models to analyze how a change in mechanical properties at the root hair initiation site can lead to star-like stress patterns in order to understand whether a stress-based feedback model can also explain the microtubule patterns seen during root hair initiation. We show that two independent mechanisms, individually or combined, can be sufficient to generate radial patterns. In the first, new material is added locally at the position of the root hair. In the second, increased tension in the initiation area provides a mechanism. Finally, we describe how a molecular model of Rho-of-plant (ROP) GTPases activation driven by auxin can position a patch of activated ROP protein basally along a 2D root epidermal cell plasma membrane, paving the way for models where mechanical and molecular mechanisms cooperate in the initial placement and outgrowth of root hairs.

Auxin Acts through MONOPTEROS to Regulate Plant Cell Polarity and Pattern Phyllotaxis.

The periodic formation of plant organs such as leaves and flowers gives rise to intricate patterns that have fascinated biologists and mathematicians alike for hundreds of years [1]. The plant hormone auxin plays a central role in establishing these patterns by promoting organ formation at sites where it accumulates due to its polar, cell-to-cell transport [2-6]. Although experimental evidence as well as modeling suggest that feedback from auxin to its transport direction may help specify phyllotactic patterns [7-12], the nature of this feedback remains unclear [13]. Here we reveal that polarization of the auxin efflux carrier PIN-FORMED 1 (PIN1) is regulated by the auxin response transcription factor MONOPTEROS (MP) [14]. We find that in the shoot, cell polarity patterns follow MP expression, which in turn follows auxin distribution patterns. By perturbing MP activity both globally and locally, we show that localized MP activity is necessary for the generation of polarity convergence patterns and that localized MP expression is sufficient to instruct PIN1 polarity directions non-cell autonomously, toward MP-expressing cells. By expressing MP in the epidermis of mp mutants, we further show that although MP activity in a single-cell layer is sufficient to promote polarity convergence patterns, MP in sub-epidermal tissues helps anchor these polarity patterns to the underlying cells. Overall, our findings reveal a patterning module in plants that determines organ position by orienting transport of the hormone auxin toward cells with high levels of MP-mediated auxin signaling. We propose that this feedback process acts broadly to generate periodic plant architectures.