Imaging criteria for assessing tumour response: RECIST, mRECIST, Cheson

AbstractMost methods define a limited number of “target” lesions to be measured and other “non-target” lesions to be evaluated qualitatively. RECIST criteria are the most widely used although other criteria have been proposed that are derived from them based on size alone, or size and attenuation. Modified RECIST (mRECIST) criteria only concern hepatocellular carcinoma and only take into account the viable portion (enhanced after injection during the arterial phase). Cheson criteria are more complex as target lesions are defined differently depending on the organ (lymph nodes, liver or spleen, other organs), and involve both CT and PET scans, as well as the clinical examination and bone marrow biopsy

A MALDI-TOF MS library for rapid identification of human commensal gut bacteria from the class Clostridia

INTRODUCTION: Microbial isolates from culture can be identified using 16S or whole-genome sequencing which generates substantial costs and requires time and expertise. Protein fingerprinting via Matrix-assisted Laser Desorption Ionization-time of flight mass spectrometry (MALDI-TOF MS) is widely used for rapid bacterial identification in routine diagnostics but shows a poor performance and resolution on commensal bacteria due to currently limited database entries. The aim of this study was to develop a MALDI-TOF MS plugin database (CLOSTRI-TOF) allowing for rapid identification of non-pathogenic human commensal gastrointestinal bacteria. METHODS: We constructed a database containing mass spectral profiles (MSP) from 142 bacterial strains representing 47 species and 21 genera within the class Clostridia. Each strain-specific MSP was constructed using >20 raw spectra measured on a microflex Biotyper system (Bruker-Daltonics) from two independent cultures. RESULTS: For validation, we used 58 sequence-confirmed strains and the CLOSTRI-TOF database successfully identified 98 and 93% of the strains, respectively, in two independent laboratories. Next, we applied the database to 326 isolates from stool of healthy Swiss volunteers and identified 264 (82%) of all isolates (compared to 170 (52.1%) with the Bruker-Daltonics library alone), thus classifying 60% of the formerly unknown isolates. DISCUSSION: We describe a new open-source MSP database for fast and accurate identification of the Clostridia class from the human gut microbiota. CLOSTRI-TOF expands the number of species which can be rapidly identified by MALDI-TOF MS

Glutathione Precursor N-Acetyl-Cysteine Modulates EEG Synchronization in Schizophrenia Patients: A Double-Blind, Randomized, Placebo-Controlled Trial

Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy

Interaction of GAG trinucleotide repeat and C-129T polymorphisms impairs expression of the glutamate-cysteine ligase catalytic subunit gene.

Glutamate cysteine ligase (GCL) catalyzes the rate-limiting step in the de novo synthesis of glutathione (GSH). The catalytic subunit (GCLC) of GCL contains a GAG trinucleotide-repeat (TNR) polymorphism within the 5'-untranslated region (5'-UTR) that has been associated with various human disorders. Although several studies suggest that this variation influences GSH content, its implication for GCLC expression remains unknown. To better characterize its functional significance, we performed reporter gene assays with constructs containing the complete GCLC 5'-UTR upstream of a luciferase gene. Transfection of these vectors into various human cell lines did not reveal any significant differences between 7, 8, 9, or 10 GAG repeats, under either basal or oxidative stress conditions. To correlate these results with the previously described down-regulation induced by the C-129T GCLC promoter polymorphism, combinations of both variations were tested. Interestingly, the -129T allele down-regulates gene expression when combined with 7 GAG but not with 8, 9, or 10 GAG TNRs. This observation was confirmed in primary fibroblast cells, in which the combination of GAG TNR 7/7 and -129C/T genotypes decreased the GCLC protein level. These results provide evidence that interaction of the two variations can efficiently impair GCLC expression and thus suggest its involvement in the pathogenesis of diseases related to GSH metabolism

Mutation screening of the glutamate cysteine ligase modifier (GCLM) gene in patients with schizophrenia.

BACKGROUND: Experimental evidences show that glutathione and its rate-limiting synthesizing enzyme, the glutamate-cysteine ligase (GCL), are involved in the pathogenesis of schizophrenia. Furthermore, genetic association has been previously reported between two single nucleotide polymorphisms lying in noncoding regions of glutamate cysteine ligase modifier (GCLM) gene, which specifies for the modifier subunit of GCL and schizophrenia. OBJECTIVE: We wanted to investigate the presence of GCLM true functional mutations, likely in linkage disequilibrium with the previously identified single nucleotide polymorphism alleles, in the same set of cases that allowed the detection of the original association signal. METHODS: We screened all the coding regions of GCLM and their intronic flanking vicinities in 353 patients with schizophrenia by direct DNA sequencing. RESULTS: Ten sequence variations were identified, five of which were not previously described. None of these DNA changes was within the GCLM coding sequence and in-silico analysis failed to indicate functional impairment induced by these variations. Furthermore, screening of normal controls and downstream statistical analyses revealed no significant relationship of any of these DNA variants with schizophrenia. CONCLUSION: It is unlikely that functional mutations in the GCLM gene could play a major role in genetic predisposition to schizophrenia and further studies will be required to assess its etiological function in the disease

Non-destructive µXRF analysis of glass and metal objects from sites in the Libyan Pre-Desert and Fazzan

This paper reports on the non-destructive analysis of 42 samples of copper alloy and glass from sites in Libya, using semi-quantitative µXRF, carried out as part of the work of the Trans-Sahara Project funded by the European Research Council. These are among the first chemical analyses to be performed on metals and glasses of any period found in Libya, and the results – though preliminary – raise some interesting possibilities. In particular, we discuss some possible indications with regard to the practice of recycling glasses, as evidenced through heterogeneous, malformed glass beads with variable quantities of lead. A glass mirror from Ghirza was also found to be backed in lead, and was probably the result of a glass-making technique still practiced in recent times in India. The metal analysis has revealed evidence of a pre-Islamic trade in brass in the Northern Sahara, as well as showing the presence of objects made from the mixing of different types of scrap metal, a process probably taking place at the Garamantian metalworking site of Saniat Jibril among other locations. The importance of further analysis of available Libyan and other North African metal artefacts and glasses for the contextualisation and extension of these findings is emphasised. يعرض هذا البحث نتائج تحليل عينات غير مدمرة من سبائك نحاسية وزجاج أخذت من مواقع ليبية وحللت باستخدام تقنية الأشعة السينية المتفلورة، ضمن مشروع "عبر الصحراء" الذي موله مجلس البحث الأوروبي . وتعد هذه التحاليل من أوائل التحاليل الكيميائية التي أجريت على المعادن والزجاج في أي فترة في ليبيا. ومع أن النتائج أوليّة، إلا أنها تطرح تساؤلات مهمة لا سيما احتمال وجود مؤشرات على ممارسة عملية تدوير الزجاج التي تظهر بوضوح من خلال عدم تجانس حبيبات الزجاج واختلاطها بكميات متفاوتة من الرصاص . كما وُجدت مرآة زجاجية في منطقة غرزة ظهر في تركيبها كمية من الرصاص، وربما نتج ذلك عن تقنية خاصة لصناعة الزجاج لا زالت تستخدم حتى الآن في الهند. لقد كشف تحليل المعادن عن أدلة تشير إلى ظهور تجارة النحاس شمال الصحراء قبل الإسلام، وهناك أدلة أخرى تظهر وجود مواد صُنعت من خليط من بقايا معادن مختلفة، ربما صُنعت في ورش الجرمنتيين، سكان ليبيا القدامى، في سانية جبريل وغيرها من المواقع . يؤكد البحث على أهمية إجراء المزيد من التحاليل على القطع الزجاجية والمعدنية المتوفرة في ليبيا وشمال إفريقيا لتطوير هذه النتائج ووضعها في سياقها المناسب

Filtering, segmentation and region classification by hyperspectral mathematical morphology of DCE-MRI series for angiogenesis imaging

ISBN : 978-1-4244-2002-5International audienceSegmenting dynamic contrast enhanced-MRI series of small animal, which are intrinsically noisy and low contrasted images with low resolution, is the aim of this paper. To do this, a segmentation method taking into account the temporal (spectral) and spatial information is presented on several series. The idea is to start from a temporal classification, and to build a probability density function of contours conditionally to this classification. Then, this function is segmented to find potentially tumorous areas. The method is presented on several series after a range normalization histogram in order to compare the series