Implication of the Autologous Immune System in BCR-ABL Transcript Variations in Chronic Myelogenous Leukemia Patients Treated with Imatinib.

International audienceImatinib and other tyrosine kinase inhibitors (TKI) have improved treatment of chronic myelogenous leukemia (CML); however, most patients are not cured. Deeper mechanistic understanding may improve TKI combination therapies to better control the residual leukemic cell population. In analyzing our patients' data, we found that many patients who otherwise responded well to imatinib therapy still showed variations in their BCR-ABL transcripts. To investigate this phenomenon, we applied a mathematical model that integrates CML and an autologous immune response to the patients' data. We define an immune window or a range of leukemic loads for which the autologous immune system induces an improved response. Our modeling results suggest that, at diagnosis, a patient's leukemic load is able to partially or fully suppress the autologous immune response developed in a majority of patients, toward the CML clone(s). Imatinib therapy drives the leukemic population into the "immune window," allowing the patient's autologous immune cells to expand and eventually mount an efficient recognition of the residual leukemic burden. This response drives the leukemic load below this immune window, allowing the leukemic population to partially recover until another weaker immune response is initiated. Thus, the autologous immune response may explain the oscillations in BCR-ABL transcripts regularly observed in patients on imatinib

Apprendre à innover dans un monde incertain

L’agriculture est aujourd’hui interpellée par la société, qui exige bien plus qu’une simple production alimentaire : aliments de qualité, services environnementaux, insertion de populations marginalisées, revitalisation des territoires ruraux, habitabilité des milieux urbains, développement de productions énergétiques… Cette ouverture des futurs agricoles incite les acteurs ruraux à expérimenter de nouveaux systèmes de production et valorisation, faisant ainsi preuve de créativité et d’obstination pour exister face aux modèles de développement dominants. Parallèlement, ces modèles dominants fondés sur la production de masse à moindre coût continuent à s’étendre, avec les promesses d’un futur basé sur les technologies vertes. Ces évolutions posent des questions. Quel type de développement durable les sociétés veulent-elles ? Comment choisir les innovations qui leur permettront d’y parvenir ? Quels rôles peuvent jouer la recherche et les politiques publiques pour favoriser l’émergence de ces innovations ? Au-delà de l’analyse des options techniques, cet ouvrage s’intéresse aux innovations sociales et institutionnelles. Il démontre que l’innovation est le résultat d’une confrontation entre des visions portées par des acteurs aux intérêts parfois divergents. Il n’y a pas de chemin unique vers un développement durable, il faut à la fois encourager l’émergence et la coexistence de différents modes d’agriculture et de systèmes alimentaires. Le succès ne dépendra pas uniquement de notre capacité à repenser les modèles existants mais également de notre volonté à nous engager dans un processus d’apprentissage dont nous sortirons forcément transformés

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Lydie Salvayre, écrivain baroque’n’roll

Dès sa petite enfance, Lydie Salvayre parle deux langues. À la maison, elle parle l’espagnol qui est la langue de ses parents, réfugiés politiques dans le sud de la France suite à la prise de pouvoir de Franco. À l’extérieur, elle parle le français. L’espagnol va devenir la langue du dedans, la langue de l’intime, des ripostes intérieures, la langue qui prend en charge tout ce que ne peut porter la langue du dehors, tout ce qui par elle est laissé de côté, tout ce qui est excessif, tout ce qui déborde, tout ce qui ne peut se rendre public, tout ce qui n’a pas d’existence légale

Création du Centre international d'études et de recherche Henri Wallon

Carpentier Claude, Risbourg Bernard, Wallet Jean-William. Création du Centre international d'études et de recherche Henri Wallon. In: Enfance, n°1, 1998. pp. 133-136

Transfer of spatial knowledge from a virtual environment to reality: Impact of route complexity and subject’s strategy on the exploration mode

The use of virtual reality as tool in the area of spatial cognition raises the question of the quality of learning transfer from a virtual to a real environment. It is first necessary to determine with healthy subjects, the cognitive aids that improve the quality of transfer and the conditions required, especially since virtual reality can be used as effective tool in cognitive rehabilitation. The purpose of this study was to investigate the influence of the exploration mode of virtual environment (Passive vs. Active) according to Route complexity (Simple vs. Complex) on the quality of spatial knowledge transfer in three spatial tasks. Ninety subjects (45 men and 45 women) participated. Spatial learning was evaluated by Wayfinding, sketch-mapping and picture classification tasks in the context of the Bordeaux district. In the Wayfinding task, results indicated that active learning in a Virtual Environment (VE) increased the performances compared to the passive learning condition, irrespective of the route complexity factor. In the Sketch-mapping task, active learning in a VE helped the subjects to transfer their spatial knowledge from the VE to reality, but only when the route was complex. In the Picture classification task, active learning in a VE when the route was complex did not help the subjects to transfer their spatial knowledge. These results are explained in terms of knowledge levels and frame/strategy of reference [SW75, PL81, TH82]