Aix-Marseille University

About: Aix-Marseille University is a education organization based out in Marseille, France. It is known for research contribution in the topics: Population & Galaxy. The organization has 24326 authors who have published 54240 publications receiving 1455416 citations. The organization is also known as: University Aix-Marseille & université d'Aix-Marseille.

Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma.

Abstract: Background Patients who have unresectable or metastatic melanoma with a BRAF V600E or V600K mutation have prolonged progression-free survival and overall survival when receiving treatment with BRAF inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year survival rates and clinical characteristics of the patients with durable benefit, we sought to review long-term data from randomized trials of combination therapy with BRAF and MEK inhibitors. Methods We analyzed pooled extended-survival data from two trials involving previously untreated patients who had received BRAF inhibitor dabrafenib (at a dose of 150 mg twice daily) plus MEK inhibitor trametinib (2 mg once daily) in the COMBI-d and COMBI-v trials. The median duration of follow-up was 22 months (range, 0 to 76). The primary end points in the COMBI-d and COMBI-v trials were progression-free survival and overall survival, respectively. Results A total of 563 patients were randomly assigned to receive dabrafenib plus trametinib (211 in the COMBI-d trial and 352 in the COMBI-v trial). The progression-free survival rates were 21% (95% confidence interval [CI], 17 to 24) at 4 years and 19% (95% CI, 15 to 22) at 5 years. The overall survival rates were 37% (95% CI, 33 to 42) at 4 years and 34% (95% CI, 30 to 38) at 5 years. In multivariate analysis, several baseline factors (e.g., performance status, age, sex, number of organ sites with metastasis, and lactate dehydrogenase level) were significantly associated with both progression-free survival and overall survival. A complete response occurred in 109 patients (19%) and was associated with an improved long-term outcome, with an overall survival rate of 71% (95% CI, 62 to 79) at 5 years. Conclusions First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. (Funded by GlaxoSmithKline and Novartis; COMBI-d ClinicalTrials.gov number, NCT01584648; COMBI-v ClinicalTrials.gov number, NCT01597908.).

European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas

Abstract: The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas, including glioblastomas. The guideline is based on the 2016 WHO classification of tumours of the central nervous system and on scientific developments since the 2014 guideline. The recommendations focus on pathological and radiological diagnostics, and the main treatment modalities of surgery, radiotherapy, and pharmacotherapy. In this guideline we have also integrated the results from contemporary clinical trials that have changed clinical practice. The guideline aims to provide guidance for diagnostic and management decisions, while limiting unnecessary treatments and costs. The recommendations are a resource for professionals involved in the management of patients with glioma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment.

Kinaesthetic role of muscle afferents in man, studied by tendon vibration and microneurography

Abstract: The characteristics of vibration-induced illusory joint movements were studied in healthy human subjects. Unseen by the subject, constant frequency vibration trains applied to the distal tendon of the Triceps or Biceps induced an almost constant velocity illusory movement of the elbow whose direction corresponded to that of a joint rotation stretching the vibrated muscle. Vibration trains of the same duration and frequency applied alternatively to the Biceps and Triceps evoked alternating flexion-extension illusory movements. During successive application of vibration trains at frequencies from 10 to 120 Hz, the perceived velocity of the illustory movements increased progressively from 10 to 70-80 Hz, then decreased from 80 to 120 Hz. The maximal perceived velocity was three times higher during alternating vibration of the Biceps and Triceps than during single muscle stimulation. Unit activity from 15 muscle spindle primary endings and five secondary endings located in Tibialis anterior and Extensor digitorum longus muscles were recorded using microneurography in order to study their responses to tendon vibration and passive and active movements of the ankle. Primary endings were all activated by low amplitude tendon vibration (0.2-0.5 mm) previously used to induce illusory movements of the elbow. The discharge of some was phase-locked with the vibration cycle up to 120 Hz, while others responded one-to-one to the vibration cycle up to 30-50 Hz, then fired in a sub-harmonic manner at higher frequencies. Secondary endings were much less sensitive to low amplitude tendon vibration. Primary and secondary ending responses to ramp and sinusoidal movements of the ankle joint were compared. During the movement, the primary ending discharge frequency was almost constant, while the secondary ending activity progressively increased. During ankle movements the primary ending discharge appeared mainly related to velocity, while some secondary activities seemed related to both movement velocity and joint angle position. Muscle spindle sensory ending responses to active and passive ankle movements stretching the receptor-bearing muscle (plantar flexion) were qualitatively and quantitatively similar. During passive reverse movements (dorsiflexion) most of the sensory endings stopped firing when their muscle shortened. Active muscle shortening (isotonic contraction) modulated differently the muscle spindle sensory ending discharge, which could stop completely, decrease or some times increase during active ankle dorsiflexion. During isometric contraction most of the muscle spindle sensory endings were activated. The characteristics of the vibration-induced illusory movements and the muscle spindle responses to tendon vibration and to active and passive joint movements strengthened the possibility of the contribution of primary endings to kinesthesia, as suggested by several previous works...

Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome

Abstract: Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by different enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at http://huttenhower.sph.harvard.edu/humann. This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future metagenomic studies.