Phase I clinical trial of the Src inhibitor dasatinib with dacarbazine in metastatic melanoma.

BackgroundSrc inhibitors sensitise melanoma cells to chemotherapy in preclinical models. The combination of dasatinib and dacarbazine was tested in a phase I trial in melanoma.MethodsPatients had ECOG performance status 0-2 and normal organ function. Dacarbazine was administered on day 1 and dasatinib on day 2 through 19 of each 21-day cycle. Both were escalated from 50 mg b.i.d. of dasatinib and 800 mg m(-2) of dacarbazine. Available pre-treatment biopsies were sequenced for BRAF, NRAS, and C-Kit mutations.ResultsDose-limiting toxicity was reached at dasatinib 70 mg b.i.d./dacarbazine 1000 mg m(-2), and was predominantly haematological. In 29 patients receiving dasatinib 70 mg b.i.d., the objective response rate (ORR) was 13.8%, the clinical benefit rate (ORR+SD) was 72.4%, the 6-month progression-free survival (PFS) was 20.7%, and the 12-month overall survival (OS) was 34.5%. Two out of three patients who were wild type for BRAF, NRAS, and c-KIT mutations had confirmed partial responses, and one had a minor response.ConclusionThe recommended phase II dose is dasatinib 70 mg b.i.d with dacarbazine 800 mg m(-2). PFS and OS data for dasatinib at 70 mg b.i.d. with dacarbazine compared favourably with historical controls. Preliminary data support evaluating tumour mutation status further as a biomarker of response

A radio census of the massive stellar cluster Westerlund 1

CONTEXT: Massive stars and their stellar winds are important for a number of feedback processes. The mass lost in the stellar wind can help determine the end-point of the star as a neutron star (NS) or a black hole (BH). However, the impact of mass loss on the post-main sequence evolutionary stage of massive stars is not well understood. Westerlund 1 is an ideal astrophysical laboratory in which to study massive stars and their winds in great detail over a large range of different evolutionary phases. AIMS: We aim to study the radio emission from Westerlund 1, in order to measure radio fluxes from the population of massive stars, and determine mass-loss rates and spectral indices where possible. METHODS: Observations were carried out in 2015 and 2016 with the Australia Telescope Compact Array (ATCA) at 5.5 and 9 GHz using multiple configurations, with maximum baselines ranging from 750 m to 6 km. RESULTS: Thirty stars are detected in the radio from the fully concatenated dataset, ten of which are Wolf-Rayet stars (WRs) (predominantly late type WN stars), five yellow hypergiants (YHGs), four red supergiants (RSGs), one luminous blue variable (LBV), the sgB[e] star W9, and several OB supergiants. New source detections in the radio are found for five WR stars, and five OB supergiants. These detections lead to evidence for three new OB supergiant binary candidates, which is inferred from derived spectral index limits. CONCLUSIONS: Spectral indices and index limits were determined for massive stars in Westerlund 1. For cluster members found to have partially optically thick emission, mass-loss rates were calculated. Under the approximation of a thermally emitting stellar wind and a steady mass-loss rate, clumping ratios were then estimated for eight WRs. Diffuse radio emission was detected throughout the cluster. Detections of knots of radio emission with no known stellar counterparts indicate the highly clumped structure of this intra-cluster medium, likely shaped by a dense cluster wind

Solar wind interaction with comet 67P: impacts of corotating interaction regions

International audienceWe present observations from the Rosetta Plasma Consortium of the effects of stormy solar wind on comet 67P/Churyumov-Gerasimenko. Four corotating interaction regions (CIRs), where the first event has possibly merged with a coronal mass ejection, are traced from Earth via Mars (using Mars Express and Mars Atmosphere and Volatile EvolutioN mission) to comet 67P from October to December 2014. When the comet is 3.1–2.7 AU from the Sun and the neutral outgassing rate ∼1025–1026 s−1, the CIRs significantly influence the cometary plasma environment at altitudes down to 10–30 km. The ionospheric low-energy (∼5 eV) plasma density increases significantly in all events, by a factor of >2 in events 1 and 2 but less in events 3 and 4. The spacecraft potential drops below −20 V upon impact when the flux of electrons increases. The increased density is likely caused by compression of the plasma environment, increased particle impact ionization, and possibly charge exchange processes and acceleration of mass-loaded plasma back to the comet ionosphere. During all events, the fluxes of suprathermal (∼10–100 eV) electrons increase significantly, suggesting that the heating mechanism of these electrons is coupled to the solar wind energy input. At impact the magnetic field strength in the coma increases by a factor of 2–5 as more interplanetary magnetic field piles up around the comet. During two CIR impact events, we observe possible plasma boundaries forming, or moving past Rosetta, as the strong solar wind compresses the cometary plasma environment. We also discuss the possibility of seeing some signatures of the ionospheric response to tail disconnection events

Airborne observations of methane emissions from rice cultivation in the Sacramento Valley of California

Airborne measurements of methane (CH4) and carbon dioxide (CO2) were taken over the rice growing region of California's Sacramento Valley in the late spring of 2010 and 2011. From these and ancillary measurements, we show that CH4 mixing ratios were higher in the planetary boundary layer above the Sacramento Valley during the rice growing season than they were before it, which we attribute to emissions from rice paddies. We derive daytime emission fluxes of CH4 between 0.6 and 2.0% of the CO2 taken up by photosynthesis on a per carbon, or mole to mole, basis. We also use a mixing model to determine an average CH 4/CO2 flux ratio of -0.6% for one day early in the growing season of 2010. We conclude the CH4/CO2 flux ratio estimates from a single rice field in a previous study are representative of rice fields in the Sacramento Valley. If generally true, the California Air Resources Board (CARB) greenhouse gas inventory emission rate of 2.7×1010g CH4/yr is approximately three times lower than the range of probable CH4 emissions (7.8-9.3×10 10g CH4/yr) from rice cultivation derived in this study. We attribute this difference to decreased burning of the residual rice crop since 1991, which leads to an increase in CH4 emissions from rice paddies in succeeding years, but which is not accounted for in the CARB inventory. © 2012. American Geophysical Union. All Rights Reserved

Quantifying sources of methane using light alkanes in the Los Angeles basin, California

Methane (CH4), carbon dioxide (CO2), carbon monoxide (CO), and C2-C5 alkanes were measured throughout the Los Angeles (L.A.) basin in May and June 2010. We use these data to show that the emission ratios of CH4/CO and CH4/CO2 in the L.A. basin are larger than expected from population-apportioned bottom-up state inventories, consistent with previously published work. We use experimentally determined CH4/CO and CH4/CO2 emission ratios in combination with annual State of California CO and CO2 inventories to derive a yearly emission rate of CH4 to the L.A. basin. We further use the airborne measurements to directly derive CH4 emission rates from dairy operations in Chino, and from the two largest landfills in the L.A. basin, and show these sources are accurately represented in the California Air Resources Board greenhouse gas inventory for CH4. We then use measurements of C2-C5 alkanes to quantify the relative contribution of other CH4 sources in the L.A. basin, with results differing from those of previous studies. The atmospheric data are consistent with the majority of CH4 emissions in the region coming from fugitive losses from natural gas in pipelines and urban distribution systems and/or geologic seeps, as well as landfills and dairies. The local oil and gas industry also provides a significant source of CH4 in the area. The addition of CH4 emissions from natural gas pipelines and urban distribution systems and/or geologic seeps and from the local oil and gas industry is sufficient to account for the differences between the top-down and bottom-up CH4 inventories identified in previously published work. Key PointsTop-down estimates of CH4 emissions in L.A. are greater than inventory estimatesEstimates of CH4 emissions from landfills in L.A. agree with CARB inventoryPipeline natural gas and/or seeps, and landfills are main sources of CH4 in L.A. ©2013. American Geophysical Union. All Rights Reserved

A survey of medical students to assess their exposure to and knowledge of renal transplantation

BACKGROUND: Within the field of renal transplantation there is a lack of qualified and trainee surgeons and a shortage of donated organs. Any steps to tackle these issues should, in part, be aimed at future doctors. METHODS: A questionnaire was distributed to final year students at a single medical school in the UK to assess their exposure to and knowledge of renal transplantation. RESULTS: Although 46% of responding students had examined a transplant recipient, only 14% had ever witnessed the surgery. Worryingly, 9% of students believed that xenotransplantation commonly occurs in the UK and 35% were unable to name a single drug that a recipient may need to take. CONCLUSIONS: This survey demonstrates a lack of exposure to, and knowledge of, the field of renal transplantation. Recommendations to address the problems with the recruitment of surgeons and donation of organs, by targeting medical students are made

Social networks and labour productivity in Europe: An empirical investigation

This paper uses firm-level data recorded in the AMADEUS database to investigate the distribution of labour productivity in different European countries. We find that the upper tail of the empirical productivity distributions follows a decaying power-law, whose exponent $\alpha$ is obtained by a semi-parametric estimation technique recently developed by Clementi et al. (2006). The emergence of "fat tails" in productivity distribution has already been detected in Di Matteo et al. (2005) and explained by means of a model of social network. Here we show that this model is tested on a broader sample of countries having different patterns of social network structure. These different social attitudes, measured using a social capital indicator, reflect in the power-law exponent estimates, verifying in this way the existence of linkages among firms' productivity performance and social network.Comment: LaTeX2e; 18 pages with 3 figures; Journal of Economic Interaction and Coordination, in pres

Photometric and spectroscopic evolution of the IIP SN 2007it to day 944

SN 2007it is a bright, Type IIP supernova which shows indications of both pre-existing and newly formed dust. The visible photometry shows a bright late-time luminosity, powered by the 0.09 M ☉ of 56Ni present in the ejecta. There is also a sudden drop in optical brightness after day 339, and a corresponding brightening in the IR due to new dust forming in the ejecta. CO and SiO emission, generally thought to be precursors to dust formation, may have been detected in the mid-IR photometry of SN 2007it. The optical spectra show stronger than average [O I] emission lines and weaker than average [Ca II] lines, which may indicate a 16-27 M ☉ progenitor, on the higher end of expected Type IIP masses. Multi-component [O I] lines are also seen in the optical spectra, most likely caused by an asymmetric blob or a torus of oxygen core material being ejected during the SN explosion. Interaction with circumstellar material prior to day 540 may have created a cool dense shell between the forward and reverse shocks where new dust is condensing. At late times there is also a flattening of the visible light curve as the ejecta luminosity fades and a surrounding light echo becomes visible. Radiative transfer models of SN 2007it spectral energy distributions indicate that up to 10–4 M ☉ of new dust has formed in the ejecta, which is consistent with the amount of dust formed in other core-collapse supernovae