A água nas Américas

A questão da água é um desafio recorrente nas Américas. Ela é cada vez mais relevante no contexto das mudanças globais: a evolução incerta das precipitações num clima que sofre mudanças, a demanda crescente de uma população mais numerosa e o desenvolvimento de atividades agrícolas ou industriais extremamente consumidoras tornam cada vez mais complexa a resolução da equação entre oferta e demanda. Ao longo das duas últimas décadas, a multiplicação dos excessos em termos de déficit ou de abundâ..

Water in the Americas

Water is a recurrent issue throughout the Americas. The context of global change renders it even more acute: the vagaries of rainfall in a changing climate, growing demand from ever increasing populations and the development of high consumption agricultural and industrial activities are making the equation between offer and demand more and more tricky to balance. Over the last two decades, extreme episodes of either drought or excess precipitation have become more frequent and led to successi..

El agua en las Américas

La cuestión del agua es un tema recurrente en las Américas. El problema es aún más acuciante en el actual contexto de cambio climático global: la incierta evolución de la pluviometría en un clima cambiante, la creciente demanda por parte de una población cada vez más numerosa y el desarrollo de actividades agrícolas o industriales que consumen grandes cantidades de agua hacen que cada vez sea más complejo resolver la ecuación entre la oferta y la demanda. En las dos últimas décadas, la multip..

The ArT\'eMiS wide-field submillimeter camera: preliminary on-sky performances at 350 microns

ArTeMiS is a wide-field submillimeter camera operating at three wavelengths simultaneously (200, 350 and 450 microns). A preliminary version of the instrument equipped with the 350 microns focal plane, has been successfully installed and tested on APEX telescope in Chile during the 2013 and 2014 austral winters. This instrument is developed by CEA (Saclay and Grenoble, France), IAS (France) and University of Manchester (UK) in collaboration with ESO. We introduce the mechanical and optical design, as well as the cryogenics and electronics of the ArTeMiS camera. ArTeMiS detectors are similar to the ones developed for the Herschel PACS photometer but they are adapted to the high optical load encountered at APEX site. Ultimately, ArTeMiS will contain 4 sub-arrays at 200 microns and 2x8 sub-arrays at 350 and 450 microns. We show preliminary lab measurements like the responsivity of the instrument to hot and cold loads illumination and NEP calculation. Details on the on-sky commissioning runs made in 2013 and 2014 at APEX are shown. We used planets (Mars, Saturn, Uranus) to determine the flat-field and to get the flux calibration. A pointing model was established in the first days of the runs. The average relative pointing accuracy is 3 arcsec. The beam at 350 microns has been estimated to be 8.5 arcsec, which is in good agreement with the beam of the 12 m APEX dish. Several observing modes have been tested, like On-The-Fly for beam-maps or large maps, spirals or raster of spirals for compact sources. With this preliminary version of ArTeMiS, we concluded that the mapping speed is already more than 5 times better than the previous 350 microns instrument at APEX. The median NEFD at 350 microns is 600 mJy.s1/2, with best values at 300 mJy.s1/2. The complete instrument with 5760 pixels and optimized settings will be installed during the first half of 2015.Comment: 11 pages, 11 figures. Presented at SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VII, June 24, 2014. To be published in Proceedings of SPIE Volume 915

Masitinib Combined with Standard Gemcitabine Chemotherapy: In Vitro and In Vivo Studies in Human Pancreatic Tumour Cell Lines and Ectopic Mouse Model

International audienceBackground: Tyrosine kinases are attractive targets for pancreatic cancer therapy because several are over-expressed, including PDGFRα/β, FAK, Src and Lyn. A critical role of mast cells in the development of pancreatic cancer has also been reported. Masitinib is a tyrosine kinase inhibitor that selectively targets c-Kit, PDGFRα/β, Lyn, and to a lesser extent the FAK pathway, without inhibiting kinases of known toxicities. Masitinib is particularly efficient in controlling the proliferation, differentiation and degranulation of mast cells. This study evaluates the therapeutic potential of masitinib in pancreatic cancer, as a single agent and in combination with gemcitabine.Methodology/Findings: Proof-of-concept studies were performed in vitro on human pancreatic tumour cell lines and then in vivo using a mouse model of human pancreatic cancer. Molecular mechanisms were investigated via gene expression profiling. Masitinib as a single agent had no significant antiproliferative activity while the masitinib/gemcitabine combination showed synergy in vitro on proliferation of gemcitabine-refractory cell lines Mia Paca2 and Panc1, and to a lesser extent in vivo on Mia Paca2 cell tumour growth. Specifically, masitinib at 10 µM strongly sensitised Mia Paca2 cells to gemcitabine (>400-fold reduction in IC50); and moderately sensitised Panc1 cells (10-fold reduction). Transcriptional analysis identified the Wnt/β-catenin signalling pathway as down-regulated in the cell lines resensitised by the masitinib/gemcitabine combination.Conclusions: These data establish proof-of-concept that masitinib can sensitise gemcitabine-refractory pancreatic cancer cell lines and warrant further in vivo investigation. Indeed, such an effect has been recently observed in a phase 2 clinical study of patients with pancreatic cancer who received a masitinib/gemcitabine combination

Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial

International audienceIntroductionNeuroinflammation is thought to be important in Alzheimer's disease pathogenesis. Mast cells are a key component of the inflammatory network and participate in the regulation of the blood-brain barrier's permeability. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. As the brain is rich in mast cells, the therapeutic potential of masitinib as an adjunct therapy to standard care was investigated.MethodsA randomised, placebo-controlled, phase 2 study was performed in patients with mild-to-moderate Alzheimer's disease, receiving masitinib as an adjunct to cholinesterase inhibitor and/or memantine. Patients were randomly assigned to receive masitinib (n = 26) (starting dose of 3 or 6 mg/kg/day) or placebo (n = 8), administered twice daily for 24 weeks. The primary endpoint was change from baseline in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) to assess cognitive function and the related patient response rate.ResultsThe rate of clinically relevant cognitive decline according to the ADAS-Cog response (increase >4 points) after 12 and 24 weeks was significantly lower with masitinib adjunctive treatment compared with placebo (6% vs. 50% for both time points; P = 0.040 and P = 0.046, respectively). Moreover, whilst the placebo treatment arm showed worsening mean ADAS-Cog, Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, and Mini-Mental State Examination scores, the masitinib treatment arm reported improvements, with statistical significance between treatment arms at week 12 and/or week 24 (respectively, P = 0.016 and 0.030; P = 0.035 and 0.128; and P = 0.047 and 0.031). The mean treatment effect according to change in ADAS-Cog score relative to baseline at weeks 12 and 24 was 6.8 and 7.6, respectively. Adverse events occurred more frequently with masitinib treatment (65% vs. 38% of patients); however, the majority of events were of mild or moderate intensity and transitory. Severe adverse events occurred at a similar frequency in the masitinib and placebo arms (15% vs. 13% of patients, respectively). Masitinib-associated events included gastrointestinal disorders, oedema, and rash.ConclusionsMasitinib administered as add-on therapy to standard care during 24 weeks was associated with slower cognitive decline in Alzheimer's disease, with an acceptable tolerance profile. Masitinib may therefore represent an innovative avenue of treatment in Alzheimer's disease. This trial provides evidence that may support a larger placebo-controlled investigation.Trial registrationClinicaltrials.gov NCT0097611