Magnetic resonance imaging for forensic age estimation in living children and young adults : a systematic review

Background The use of magnetic resonance imaging (MRI) in forensic age estimation has been explored extensively during the past decade. Objective To synthesize the available MRI data for forensic age estimation in living children and young adults, and to provide a comprehensive overview that can guide age estimation practice and future research. Materials and Methods MEDLINE, Embase and Web of Science were searched. Additionally, cited and citing articles and study registers were searched. Two authors independently selected articles, conducted data extraction, and assessed risk of bias. Study populations including living subjects up to 30 years were considered. Results Fifty-five studies were included in qualitative analysis and 33 in quantitative analysis. Most studies suffered from bias, including relatively small European (Caucasian) populations, varying MR-approaches and varying staging techniques. Therefore, pooling of the age distribution data was not appropriate. Reproducibility of staging was remarkably lower in clavicles than in any other anatomical structure. Age estimation performance was in line with the gold standard, which uses radiographs, with mean absolute errors ranging from 0.85 to 2.0 years. The proportion of correctly classified minors ranged from 65% to 91%. Multi-factorial age estimation performed better than based on a single anatomical site. Conclusion More multi-factorial age estimation studies are necessary, together with studies testing if the MRI data can safely be pooled. The current review results can guide future studies, help medical professionals to decide on the preferred approach for specific cases, and help judicial professionals to interpret the evidential value of age estimation results

Elucidation of the Mode of Action of a New Antibacterial Compound Active against Staphylococcus aureus and Pseudomonas aeruginosa.

Nosocomial and community-acquired infections caused by multidrug resistant bacteria represent a major human health problem. Thus, there is an urgent need for the development of antibiotics with new modes of action. In this study, we investigated the antibacterial characteristics and mode of action of a new antimicrobial compound, SPI031 (N-alkylated 3, 6-dihalogenocarbazol 1-(sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol), which was previously identified in our group. This compound exhibits broad-spectrum antibacterial activity, including activity against the human pathogens Staphylococcus aureus and Pseudomonas aeruginosa. We found that SPI031 has rapid bactericidal activity (7-log reduction within 30 min at 4x MIC) and that the frequency of resistance development against SPI031 is low. To elucidate the mode of action of SPI031, we performed a macromolecular synthesis assay, which showed that SPI031 causes non-specific inhibition of macromolecular biosynthesis pathways. Liposome leakage and membrane permeability studies revealed that SPI031 rapidly exerts membrane damage, which is likely the primary cause of its antibacterial activity. These findings were supported by a mutational analysis of SPI031-resistant mutants, a transcriptome analysis and the identification of transposon mutants with altered sensitivity to the compound. In conclusion, our results show that SPI031 exerts its antimicrobial activity by causing membrane damage, making it an interesting starting point for the development of new antibacterial therapies

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

Guidelines and Recommendations on Yeast Cell Death Nomenclature

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research

Guidelines and recommendations on yeast cell death nomenclature

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cel-lular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the defi-nition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differ-ential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death rou-tines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the au-thors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the pro-gress of this vibrant field of research

Dental age estimation in sub-adults: striving for an optimal approach.

Increasing global human migration, raises management concerns in the countries where immigrants seek shelter. A special protective status must be given to immigrating unaccompanied children. Therefore, most national laws enforce specialized medical investigations to get proof of the age of unaccompanied youngsters with no, or lacking official identification documents and claiming to be minors. Dental age estimation in this particular age group relies on the only dental age predictor(s) available, namely the developing third molar(s). Hence, scientific correct dental age estimations in sub-adults, especially when originating from distant countries and diverse biological origin are requested. The general research aim was to optimize dental age estimation based on third molar development.Panoramic radiographs were retrospectively and cross-sectional sampled to collect data registering third molar development. For that registration, two techniques were described. The sequence of third molar development was divided in succeeding stages, and the observed third molar development was classified in the corresponding stage. Otherwise, the dimensions of third molars increase during its maturation and measures of the observed third molar sizes were registered. In the current thesis, both registration techniques were compared. Third molar stages (categorical data) were best related to age and provided the most accurate age predictions compared to all collected tooth measurements and ratios of tooth measurements (continuous data). Combining the scored third molar stages with tooth measurements or ratios did not contribute to a clinical relevant information gain for age prediction. Multiple tooth development staging techniques were reported, based on the described and considered borderlines between succeeding stages the quantity of stages covering the third molar development process differs between techniques. Therefore, it was studied if the number of stages used in a staging technique is influencing the age prediction performances. The number of stages utilized in the third molar registration technique slightly influenced the age predictions. The choice of third molar development registration technique has to depend on its stages described for the developmental period of interest and should not compromise the feasibility of correctly registering all these stages.The classical approach for age estimation uses regression analysis to model the collected reference data. Drawbacks of this technique concern the age distribution of the residuals, the high correlation between the independent variables, often observed missing values of the independent variables, and a systematic bias in the age predictions. Therefore, a Bayesian approach of age estimation on third molar development was established in the current study. The age prediction performances of both approaches were compared. Both models provided similar accuracy, precision and coverage in age estimation outcome. The Bayesian approach reduced the bias that is typically present inthe regression models. The age of juveniles was less overestimated, yielding a better discrimination between subjects older or younger than 18 years. Moreover, the Bayesian model integrated all available third molar information.Sub-adult age estimations are mostly requested to discriminate a child from an adult during migration and asylum procedures. Due to the migration aspect, frequently the age of an applicant with a particular geographical and biologic origin was estimated using methods or models developed on a reference sample, including subjects with unlike origin. It was investigated whether differences in third molar development between populations with different geographic and biological origin exist. Therefore, third molar development was analysed and compared on 13 country-specific samples using a factor analysis. Differences in third molar development between countries exist, but they were not constant over age and varied in an unordered way. Because the magnitude of the differences turned out to be small there was no evidence for important differences in third molar development between the countries. Age estimation models developed on a particular country-specific reference sample were validated on their age prediction performances using a validation sample from a different geographic and biological origin as the reference sample. Validated on 13 country-specific databases using information from Belgium, or all countries pooled together changes the difference between observed and predicted age obtained on country-specific information only slightly. For the adult-juvenile discrimination, the Belgium reference model provided a maximal advantage of the doubt to investigated unaccompanied minor fugitives. The reference model based on all pooled countries, substituted the country-specific reference model most accurately in sub-adults. The age prediction performances of age estimation models constructed on a single age-related variable are possibly ameliorated, adding age-related information of one or more variables present in the considered period of life. Therefore, reference samples registering at a specific moment third molar development, as well as tooth morphological or skeletal age-related variables, were collected, modelled and validated. Due to the inherent image quality of panoramic radiographs tooth morphological measurements based on secondary dentine apposition, could only be achieved on a restricted sample. Clinically the gain in age prediction accuracy was negligible when adding the time consuming additional tooth morphological measurements to the staged third molar development. On cephalometric radiographs the skeletal age predicting variable(s) and related registration systems providing the most information on age were cervical vertebrae scoring systems. Combining the information from cervical vertebrae and third molars improved the age predictions drastically in the period of early third molar development. In sub-adults no, or a negligible, gain in accuracy of age prediction was obtained. In an optimal approach, dental age estimations in sub-adults are based on the radiologically observed developmental status or the absence, of each third molar. The observed information is registered according to a staging technique. The collected reference information is modeled as dependent ordinal data in a multivariate Bayesian approach. Despite detected country-specific differences in third molar development, the clinical impact on age estimation is minimal. Based on an ongoing country-specific data collection, a quantification of the maximal difference in prediction error using not county-specific reference information is established. Further on, the Belgium reference information classifies more juveniles compared to country-specific information and is recommended in lack of a country-specific reference model for age estimations of young unaccompanied fugitives.General Introduction 15 Objectives of the research 35 Registration of third molar development: Influence of measurements versus stages on age estimation 41 Staged third molar development registration: Influence of the number of stages on age estimation. 53 Statistical modeling of third molar development data: Influence of regression analyses versus Bayesian approach on age estimation 65 Collection and comparison of 13 country-specific third molar development databases. 79 Comparison of age estimation based on 13 country-specific third molar development databases. 93 Influence of tooth morphological age predictors on age estimation based on third molar development. 111 Influence of skeletal age predictors on age estimation based on third molar development. 121 General discussion and conclusion 135nrpages: 175status: publishe