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.

Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis

Abstract: Summary Background Obesity has been linked to increased mortality in several cancer types; however, the relation between obesity and survival outcomes in metastatic melanoma is unknown The aim of this study was to examine the association between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma who received targeted therapy, immunotherapy, or chemotherapy Methods This retrospective study analysed independent cohorts of patients with metastatic melanoma assigned to treatment with targeted therapy, immunotherapy, or chemotherapy in randomised clinical trials and one retrospective study of patients treated with immunotherapy Patients were classified according to BMI, following the WHO definitions, as underweight, normal, overweight, or obese Patients without BMI and underweight patients were excluded The primary outcomes were the associations between BMI and progression-free survival or overall survival, stratified by treatment type and sex We did multivariable analyses in the independent cohorts, and combined adjusted hazard ratios in a mixed-effects meta-analysis to provide a precise estimate of the association between BMI and survival outcomes; heterogeneity was assessed with meta-regression analyses Analyses were done on the predefined intention-to-treat population in the randomised controlled trials and on all patients included in the retrospective study Findings The six cohorts consisted of a total of 2046 patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy between Aug 8, 2006, and Jan 15, 2016 1918 patients were included in the analysis Two cohorts containing patients from randomised controlled trials treated with targeted therapy (dabrafenib plus trametinib [n=599] and vemurafenib plus cobimetinib [n=240]), two cohorts containing patients treated with immunotherapy (one randomised controlled trial of ipilimumab plus dacarbazine [n=207] and a retrospective cohort treated with pembrolizumab, nivolumab, or atezolizumab [n=331]), and two cohorts containing patients treated with chemotherapy (two randomised controlled trials of dacarbazine [n=320 and n=221]) were classified according to BMI as normal (694 [36%] patients), overweight (711 [37%]), or obese (513 [27%]) In the pooled analysis, obesity, compared with normal BMI, was associated with improved survival in patients with metastatic melanoma (average adjusted hazard ratio [HR] 0·77 [95% CI 0·66–0·90] for progression-free survival and 0·74 [0·58–0·95] for overall survival) The survival benefit associated with obesity was restricted to patients treated with targeted therapy (HR 0·72 [0·57–0·91] for progression-free survival and 0·60 [0·45–0·79] for overall survival) and immunotherapy (HR 0·75 [0·56–1·00] and 0·64 [0·47–0·86]) No associations were observed with chemotherapy (HR 0·87 [0·65–1·17, p interaction =0·61] for progression-free survival and 1·03 [0·80–1·34, p interaction =0·01] for overall survival) The association of BMI with overall survival for patients treated with targeted and immune therapies differed by sex, with inverse associations in men (HR 0·53 [0·40–0·70]), but no associations observed in women (HR 0·85 [0·61–1·18, p interaction =0·03]) Interpretation Our results suggest that in patients with metastatic melanoma, obesity is associated with improved progression-free survival and overall survival compared with those outcomes in patients with normal BMI, and that this association is mainly seen in male patients treated with targeted or immune therapy These results have implications for the design of future clinical trials for patients with metastatic melanoma and the magnitude of the benefit found supports further investigation of the underlying mechanism of these associations Funding ASCO/CCF Young Investigator Award, ASCO/CCF Career Development Award, MD Anderson Cancer Center (MDACC) Melanoma Moonshot Program, MDACC Melanoma SPORE, and the Dr Miriam and Sheldon G Adelson Medical Research Foundation

Search for direct production of charginos, neutralinos and sleptons in final states with two leptons and missing transverse momentum in pp collisions at √s = 8TeV with the ATLAS detector

Abstract: Search for direct production of charginos, neutralinos and sleptons in final states with two leptons and missing transverse momentum in pp collisions at root s=8TeV with the ATLAS detector

Comparative genomic analysis of the thermophilic biomass-degrading fungi Myceliophthora thermophila and Thielavia terrestris

Abstract: Thermostable enzymes and thermophilic cell factories may afford economic advantages in the production of many chemicals and biomass-based fuels. Here we describe and compare the genomes of two thermophilic fungi, Myceliophthora thermophila and Thielavia terrestris. To our knowledge, these genomes are the first described for thermophilic eukaryotes and the first complete telomere-to-telomere genomes for filamentous fungi. Genome analyses and experimental data suggest that both thermophiles are capable of hydrolyzing all major polysaccharides found in biomass. Examination of transcriptome data and secreted proteins suggests that the two fungi use shared approaches in the hydrolysis of cellulose and xylan but distinct mechanisms in pectin degradation. Characterization of the biomass-hydrolyzing activity of recombinant enzymes suggests that these organisms are highly efficient in biomass decomposition at both moderate and high temperatures. Furthermore, we present evidence suggesting that aside from representing a potential reservoir of thermostable enzymes, thermophilic fungi are amenable to manipulation using classical and molecular genetics.

The dependence of Type Ia Supernovae luminosities on their host galaxies

Abstract: (Abridged) Precision cosmology with Type Ia supernovae (SNe Ia) makes use of the fact that SN Ia luminosities depend on their light-curve shapes and colours. Using Supernova Legacy Survey (SNLS) and other data, we show that there is an additional dependence on the global characteristics of their host galaxies: events of the same light-curve shape and colour are, on average, 0.08mag (~4.0sigma) brighter in massive host galaxies (presumably metal-rich) and galaxies with low specific star-formation rates (sSFR). SNe Ia in galaxies with a low sSFR also have a smaller slope ("beta") between their luminosities and colours with ~2.7sigma significance, and a smaller scatter on SN Ia Hubble diagrams (at 95% confidence), though the significance of these effects is dependent on the reddest SNe. SN Ia colours are similar between low-mass and high-mass hosts, leading us to interpret their luminosity differences as an intrinsic property of the SNe and not of some external factor such as dust. If the host stellar mass is interpreted as a metallicity indicator, the luminosity trends are in qualitative agreement with theoretical predictions. We show that the average stellar mass, and therefore the average metallicity, of our SN Ia host galaxies decreases with redshift. The SN Ia luminosity differences consequently introduce a systematic error in cosmological analyses, comparable to the current statistical uncertainties on parameters such as w. We show that the use of two SN Ia absolute magnitudes, one for events in high-mass (metal-rich) galaxies, and one for events in low-mass (metal-poor) galaxies, adequately corrects for the differences. Cosmological fits incorporating these terms give a significant reduction in chi^2 (3.8-4.5sigma). We conclude that future SN Ia cosmological analyses should use a correction of this (or similar) form to control demographic shifts in the galaxy population.

On the growth and form of cortical convolutions

Abstract: A 3D-printed fetal brain undergoes constrained expansion to reproduce the shape of the human cerebral cortex. The soft gels of the model swell in solvent, mimicking cortical growth and revealing the mechanical origin of the brain’s folded geometry.