Informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry (GCxGC-HRMS)

This paper describes informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography (GCxGC) and high-resolution mass spectrometry (HRMS). GCxGC-HRMS analysis produces large data sets that are rich with information, but highly complex. The size of the data and volume of information requires automated processing for comprehensive cross-sample analysis, but the complexity poses a challenge for developing robust methods. The approach developed here analyzes GCxGC-HRMS data from multiple samples to extract a feature template that comprehensively captures the pattern of peaks detected in the retention-times plane. Then, for each sample chromatogram, the template is geometrically transformed to align with the detected peak pattern and generate a set of feature measurements for cross-sample analyses such as sample classification and biomarker discovery. The approach avoids the intractable problem of comprehensive peak matching by using a few reliable peaks for alignment and peak-based retention-plane windows to define comprehensive features that can be reliably matched for cross-sample analysis. The informatics are demonstrated with a set of 18 samples from breast-cancer tumors, each from different individuals, six each for Grades 1-3. The features allow classification that matches grading by a cancer pathologist with 78% success in leave-one-out cross-validation experiments. The HRMS signatures of the features of interest can be examined for determining elemental compositions and identifying compounds.

Intellectual outcome, motor skills and BMI of children with congenital hypothyroidism: a population-based study

AIM: To evaluate intellectual outcome, motor skills and anthropometric data of children with congenital hypothyroidism (CH). METHODS: Children with permanent CH who were born in 1999 in Bavaria were eligible for this prospective, population-based study. Cognitive performance was evaluated by the Kaufman Assessment Battery for Children and motor skills were assessed by the motor test, Motoriktest für vier-bis sechsjahrige Kinder (MOT) 4-6. RESULTS: Eighteen of 21 eligible children participated (86%). Median age of the children was 5.5 years (range 4.9-5.8). Treatment with levothyroxine was started after a median of 7.2 days (range 4-15) with a median dose of 12.0 microg/kg (range 7.2-17.0). Mean intelligence quotient (IQ) of the children was 100.4 (standard deviation [SD] 10.1): no children had IQ values below the normal range. Reactivity and speed of movement were significantly reduced in children with CH. Children with an initial thyroid-stimulating hormone (TSH) value of >200 mU/L performed significantly worse than children with TSH value of intellectual development was normal.

Intellectual Property and Traditional Cultural Expressions in a Digital Environment

In the face of increasing globalisation, and a collision between global communication systems and local traditions, this book offers innovative trans-disciplinary analyses of the value of traditional cultural expressions (TCE) and suggests appropriate protection mechanisms for them. It combines approaches from history, philosophy, anthropology, sociology and law, and charts previously untravelled paths for developing new policy tools and legal designs that go beyond conventional copyright models. Its authors extend their reflections to a consideration of the specific features of the digital environment, which, despite enhancing the risks of misappropriation of traditional knowledge and creativity, may equally offer new opportunities for revitalising indigenous peoples' values and provide for the sustainability of TCE.This book will appeal to scholars interested in multidisciplinary analyses of the fragmentation of international law in the field of intellectual property and traditional cultural expressions. It will also be valuable reading for those working on broader governance and human rights issues.

Elevated serum triiodothyronine and intellectual and motor disability with paroxysmal dyskinesia caused by a monocarboxylate transporter 8 gene mutation

Monocarboxylate transporter 8 (MCT8 or SLC16A2) is important for the neuronal uptake of triiodothyronine (T3) in its function as a specific and active transporter of thyroid hormones across the cell membrane, thus being essential for human brain development. We report on a German male with Allan-Herndon-Dudley syndrome presenting with severe intellectual and motor disability, paroxysmal dyskinesia combined with truncal muscular hypotonia, and peripheral muscular hypertonia at his current age of 9 years. Additionally, the patient has a lesion in the left putamen region revealed by magnetic resonance imaging and elevated serum T3 levels. The male appeared to have a hemizygous mutation (R271H) in the MCT8 gene that was sequenced directly from genomic DNA and occurred de novo in the maternal germline, as both his mother and his sister were not carriers of the mutation. Ruling out a common polymorphism, 50 normal individuals of the same ethnic background did not harbour the mutation. The identified MCT8 gene mutation (R271H) is very likely to be the genetic cause for neuronal hypothyroidism despite elevated serum T3 levels.