Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for Philadelphia chromosome-positive leukemia.

Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, both as first-line therapy and after imatinib intolerance or resistance. While generally well tolerated, dasatinib has been associated with a higher risk for pleural effusions. Frequency, risk factors, and outcomes associated with pleural effusion were assessed in two phase 3 trials (DASISION and 034/Dose-optimization) and a pooled population of 11 trials that evaluated patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with dasatinib (including DASISION and 034/Dose-optimization). In this largest assessment of patients across the dasatinib clinical trial program (N=2712), pleural effusion developed in 6-9% of patients at risk annually in DASISION, and in 5-15% of patients at risk annually in 034/Dose-optimization. With a minimum follow up of 5 and 7 years, drug-related pleural effusion occurred in 28% of patients in DASISION and in 33% of patients in 034/Dose-optimization, respectively. A significant risk factor identified for developing pleural effusion by a multivariate analysis was age. We found that overall responses to dasatinib, progression-free survival, and overall survival were similar in patients who developed pleural effusion and in patients who did not. clinicaltrials.gov identifier 00481247; 00123474

Systems with jumps : theory and applications

Introduced in the eigthies, the systems with jumps, also called at the beginning hybrid systems, can efficiently modelize a grea t number of physical systems subject to random jumps in their dynamics . A manoeuvering fighting aircraft, widely studied in th e litterature, is a good illustration of this type of systems . Stability, optimal control and stochastic filtering were the major areas o f study for these models . In fact this modelization results from a combination of three ingredients : diffusion, jumps and deterministi c processes . When restricting ourselves to the first two kinds of processes, we consider models with stochastic diffusions . So, after having introduced the general mathematical representation for such processes, we consider in this article a typica l application in aerospace, the target tracking, to show the significant improvements in performance brought by this approach . When then conclude, after having recalled the various contributions brought by our group on the stochastic diffusions during the last fifteen years .Introduits dans les années quatre vingt, les systèmes à sauts, plus connus à l'origine sous le nom de systèmes hybrides, offrent un cadre mathématique idéal pour l'étude de systèmes physiques caractérisés par des modifications (sauts), brutales et aléatoires de leur dynamique. Un des exemples les plus couramment rencontrés dans la littérature est celui d'un avion de chasse effectuant diverses manoeuvres. La stabilité, la commande optimale et le filtrage stachastique ont été les trois principaux domaines d'études de ces modèles. Cette modélisation résulte en fait d'un mélange de trois constituants élémentaires que sont les processus de diffusion, les processus à sauts et les processus déterministes. En se restreignant aux deux premiers ingrédients, nous parlerons de modèles à diffusions aléatoires. Après avoir introduit la modélisation mathématique de tels processus, nous nous intéressons dans cet article à une application type, la poursuite de trajectoire, afin de montrer les améliorations significatives qu'apporte cette approche. Enfin nous conclurons, non sans avoir rappelé les différents travaux accomplis sur les diffusions aléatoires dans notre groupe, au cours de ces quinze dernières années

Asymmetric Distribution of Lunar Impact Basins Caused by Variations in Target Properties

Maps of crustal thickness derived from NASA's Gravity Recovery and Interior Laboratory (GRAIL) mission revealed more large impact basins on the nearside hemisphere of the Moon than on its farside. The enrichment in heat-producing elements and prolonged volcanic activity on the lunar nearside hemisphere indicate that the temperature of the nearside crust and upper mantle was hotter than that of the farside at the time of basin formation. Using the iSALE-2D hydrocode to model impact basin formation, we found that impacts on the hotter nearside would have formed basins up to two times larger than similar impacts on the cooler farside hemisphere. The size distribution of lunar impact basins is thus not representative of the earliest inner Solar system impact bombardment

Supplemental Information For: Asymmetric Distribution of Lunar Impact Basins Caused by Variations in Target Properties

Maps of crustal thickness derived from NASA's Gravity Recovery and Interior Laboratory (GRAIL) mission revealed more large impact basins on the nearside hemisphere of the Moon than on its farside. The enrichment in heat-producing elements and prolonged volcanic activity on the lunar nearside hemisphere indicate that the temperature of the nearside crust and uppermantle was hotter than that of the farside at the time of basin formation. Using the iSALE-2D hydrocode to model impact basin formation, we found that impacts on the hotter nearside would have formed basins up to two times larger than similar impacts on the cooler farside hemisphere. The size distribution of lunar impact basins is thus not representative of the earliest inner Solar system impact bombardmen

Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation

BACKGROUND: Mycoplasmas are the smallest microorganisms capable of self-replication. Our previous studies show that some mycoplasmas are able to induce malignant transformation of host mammalian cells. This malignant transformation is a multistage process with the early infection, reversible and irreversible stages, and similar to human tumor development in nature. The purpose of this study is to explore mechanisms for this malignant transformation. METHODS: To better understand mechanisms for this unique process, we examined gene expression profiles of C3H cells at different stages of the mycoplasma-induced transformation using cDNA microarray technology. A total of 1185 genes involved in oncogenesis, apoptosis, cell growth, cell-cycle regulation, DNA repair, etc. were examined. Differences in the expression of these genes were compared and analyzed using the computer software AtlasImage. RESULTS: Among 1185 genes screened, 135 had aberrant expression at the early infection stage, 252 at the reversible stage and 184 at the irreversible stage. At the early infection stage, genes with increased expression (92 genes) were twice more than those with decreased expression (42 genes). The global gene expression at the reversible stage appeared to be more volatile than that at any other stages but still resembled the profile at the early infection stage. The expression profile at the irreversible stage shows a unique pattern of a wide range of expression levels and an increased number of expressing genes, especially the cancer-related genes. Oncogenes and tumor suppressors are a group of molecules that showed significant changes in expression during the transformation. The majority of these changes occurred in the reversible and irreversible stages. A prolonged infection by mycoplasmas lead to the expression of more cancer related genes at the irreversible stage. CONCLUSION: The results indicate that the expression profiles correspond with the phenotypic features of the cells in the mycoplasma induced transformation process. The early mycoplasma infection stage shares a common phenomenon with many other acute infections, genes with increased expression significantly outnumbering those with decreased expression. The reversible stage is a transition stage between benignancy and malignancy at the molecular level. Aberrant expression of oncogenes and tumor repressors plays a key role in mycoplasma-induced malignant transformation

Long-lived magnetism from solidification-driven convection on the pallasite parent body.

Palaeomagnetic measurements of meteorites suggest that, shortly after the birth of the Solar System, the molten metallic cores of many small planetary bodies convected vigorously and were capable of generating magnetic fields. Convection on these bodies is currently thought to have been thermally driven, implying that magnetic activity would have been short-lived. Here we report a time-series palaeomagnetic record derived from nanomagnetic imaging of the Imilac and Esquel pallasite meteorites, a group of meteorites consisting of centimetre-sized metallic and silicate phases. We find a history of long-lived magnetic activity on the pallasite parent body, capturing the decay and eventual shutdown of the magnetic field as core solidification completed. We demonstrate that magnetic activity driven by progressive solidification of an inner core is consistent with our measured magnetic field characteristics and cooling rates. Solidification-driven convection was probably common among small body cores, and, in contrast to thermally driven convection, will have led to a relatively late (hundreds of millions of years after accretion), long-lasting, intense and widespread epoch of magnetic activity among these bodies in the early Solar System.The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement No. 320750, the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 312284, the Natural Environment Research Council, Fundación ARAID and the Spanish MINECO MAT2011-23791.This is the accepted manuscript. The final version is available from Nature at http://www.nature.com/nature/journal/v517/n7535/full/nature14114.html