The 2007 WHO classification of tumours of the central nervous system

The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book', the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wid

The 2007 WHO Classification of Tumours of the Central Nervous System

The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide

Analysis of phone confusion matrices in a manually annotated French-German learner corpus

International audienceThis paper presents an analysis of the non-native and native pronunciations observed in a phonetically annotated bilingual French-German corpus. After a forced-choice automatic annotation a large part of the corpus was checked and corrected manually on the phone level which allows a detailed comparison of the realized sounds with the expected sounds. The analysis is reported in terms of phone confusion matrices for selected error-prone classes of sounds. It revealed that German learners of French have most problems with obstruents in word-final position whereas French learners of German show complex interferences with the vowel contrasts for length and quality. Finally, the correct pronunciation rate of the sounds, for several phonetic classes, is analyzed with respect to the learner's level, and compared to native pronunciations. One outcome is that different sound classes show different correct rates over the proficiency levels. For the German data the frequently occurring syllabic [=n] is a prime indicator of the proficiency level

Constitution d'un Corpus de Français Langue Etrangère destiné aux Apprenants Allemands

International audienceLa plupart des corpus en langue se focalisent sur les phénomènes linguistiques écrits et concernent l’anglais (voir le site web : « Learner corpora around the world » de l’Université de Louvain - Belgique). La recherche phonétique sur l’acquisition d’une L2 est généralement orientée vers l’étude des phénomènes segmentaux et la plupart des études ont également l’anglais comme langue cible. Les modèles de parole en L2 actuels - voir par exemple Speech Learning Model (Flege, 1995) ou Best’s Perceptual Assimilation Model (Best, 1995) – négligent bien souvent les aspects prosodiques. Notre étude concerne le français en tant que langue seconde et s’inscrit dans un projet plus vaste mené en partenariat avec une université allemande, dont l’un des buts est le développement de l’apprentissage des langues par ordinateur. (Projet ANR-DFG – Agence Nationale de la Recherche et Deutsche Forschungsgemeinschaft attribué à l’équipe Parole du LORIA UMR 7503, Nancy – France et à l’Equipe de Linguistique Computationnelle et de Phonétique FR 4.7 de l’Université de la Sarre Sarrebruck – Allemagne) dans lequel le français et l’allemand sont des langues cibles. Pour la paire allemand-français, peu de corpus parallèles sont disponibles. Nous présentons ici l’élaboration d’un corpus de productions orales de locuteurs natifs et non natifs pour la paire allemand-français. Notre corpus entend mettre au jour les déviations phonétiques et phonologiques que les locuteurs allemands produisent lorsqu’ils apprennent le français. Ce travail s’insère dans un projet plus global, Ce projet entend étudier les difficultés que les locuteurs français rencontrent lorsqu’ils apprennent l’allemand, et réciproquement. Aussi, cinquante locuteurs allemands seront recrutés dans des milieux universitaires et scolaires (niveau lycée) en Allemagne et cinquante locuteurs français dans les mêmes milieux en France. Il s’agit pour les deux populations de produire d’une part le corpus en langue étrangère (en langue française pour les locuteurs allemands et en langue allemande pour les locuteurs français) mais également le corpus en langue maternelle (en allemand pour les allemands et en français pour les français). Les corpus ainsi obtenus devraient nous permettre d’identifier les difficultés que les locuteurs allemands ou français rencontrent lorsqu’ils apprennent le français ou l’allemand. Les données de contrôle sont doubles puisque l’on pourra à la fois se référer aux productions des apprenants dans leur langue maternelle (ici l’allemand), mais également à celles de locuteurs natifs (ici germanophones). Nous ne présenterons ici que la constitution du corpus en français

Designing a Bilingual Speech Corpus for French and German Language Learners: a Two-Step Process

International audienceWe present the design of a corpus of native and non-native speech for the language pair French-German, with a special emphasis on phonetic and prosodic aspects. To our knowledge there is no suitable corpus, in terms of size and coverage, currently available for the target language pair. To select the target L1-L2 interference phenomena we prepare a small preliminary corpus (corpus1), which is analyzed for coverage and cross-checked jointly by French and German experts. Based on this analysis, target phenomena on the phonetic and phonological level are selected on the basis of the expected degree of deviation from the native performance and the frequency of occurrence. 14 speakers performed both L2 (either French or German) and L1 material (either German or French). This allowed us to test, recordings duration, recordings material, the performance of our automatic aligner software. Then, we built corpus2 taking into account what we learned about corpus1. The aims are the same but we adapted speech material to avoid too long recording sessions. 100 speakers will be recorded. The corpus (corpus1 and corpus2) will be prepared as a searchable database, available for the scientific community after completion of the project

A Very Large Number of GABAergic Neurons Are Activated in the Tuberal Hypothalamus during Paradoxical (REM) Sleep Hypersomnia

We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD67 in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD+, Fos-ir/MCH+, and GAD+/MCH+ double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD+ neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit

Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study

Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age