Phase II study of paclitaxel combined with capecitabine as second-line treatment for advanced gastric carcinoma after failure of cisplatin-based regimens

Purpose To determine the safety and the efficacy of paclitaxel and capecitabine as second-line combination chemotherapy after failure of platinum regimens in advanced gastric cancer. Methods Patients with histologically proven gastric cancer and measurable metastatic disease received capecitabine 825 mg/m2 twice daily (1,650 mg/m2 per day) on days 1–14 and paclitaxel 175 mg/m2 by intravenous infusion on day 1 every 3 weeks until disease progression or unacceptable toxicities. Results Between June 2003 and October 2005, 26 patients, of median age 59 years (range 41–84 years) were included in the study and were treated by paclitaxel/capecitabine combination. Overall response rate was 34.6% (95%CI = 17.2–55.7%) with one complete response and 42.3% (95%CI = 17.2–55.7%) of patients achieved a stable disease. Median progression-free survival was 4.5 months (95%CI = 4–4.5 months). Median overall survival was 7.5 months (95%CI = 6–10 months). Cumulated overall survival including cisplatin regimens was 15.5 months (95%CI = 11–18 months). Grade 3/4 adverse events included alopecia (30.8%), neutropenia (11.5%), hand foot skin reaction (11.5%), neuropathy (11.5%), arthralgias (7.5%), and anemia (3.8%). Conclusions Paclitaxel and capecitabine combination was safe and effective in advanced gastric cancer after failure of cisplatin regimens. The cumulated overall survival of 15.5 months suggests a particular interest of taxanes in second-line treatment after failure of platinum salts

L’immunothérapie dans le cancer du rein : un développement clinique en plein essor

CONTEXT: Nivolumab, an anti-PD1 immune control point inhibitor, is the first treatment that has improved the overall survival of patients after first-line metastatic renal cell carcinoma in 2015. Over the past two years, a large number of trials on these treatments and the interest of associations are being evaluated. OBJECTIVE: In this article, we propose to summarize the clinical development of checkpoint inhibitors to assess the direction of clinical research in this area. DOCUMENTARY SOURCE: A systematic review of the literature was performed in PubMed/Medline database and Meeting Library Asco by searching for articles in French or English published on immunotherapy in renal cell carcinoma. The research was limited to abstracts and articles published from 2014 to 2017. SELECTION OF TRIALS: We identified 349 publications and abstracts and selected 17 references from prospective studies. RESULTS: Recent data on checkpoint inhibitors, as well as their combination with tyrosine kinase inhibitors or with anti-angiogenic agents or with indoleamine 2, 3-dioxygenase 1 in renal cell carcinoma and the latest advances in vaccine therapy have been reported. CONCLUSION: In 2017, immunotherapy combined with other treatments is likely to lead to a paradigm shift in the clinical management of patients. The combination of nivolumab and ipilimumab in the first line will revolutionize the therapeutic management of patients with metastatic renal cell carcinoma

Prise en charge des métastases du cancer du rein

The management of metastatic renal cell carcinoma had changed over the last ten years with the apparition of new treatments and advances in surgery and ablative techniques. The therapies for metastatic patients have also been personalized and different prognostic groups have been established to adapt the treatment to the severity of the disease. Surgical excision, radiotherapy or ablative therapy could be proposed for patients with isolated metastasis and good condition to delay the systemic therapy initiation. Until 2006, in case of metastatic renal cell carcinoma, immunotherapy (IL-2 and TNF-alpha) was proposed. Targeted therapies acting on angiogenesis mechanisms have also been developed. Recently, immunotherapy has revolutionized the therapeutic management and has improved the overall survival of patients with metastatic renal carcinoma. For each patient, a multidisciplinary management is organized with a personal therapeutic project. This global management needs coordination with the medical team and also need a good communication with the patient, his entourage and his doctor

A System Trade Study of Remote Infrared Imaging for Space Shuttle Reentry

A trade study reviewing the primary operational parameters concerning the deployment of imaging assets in support of the Hypersonic Thermodynamic Infrared Measurements (HYTHIRM) project was undertaken. The objective was to determine key variables and constraints for obtaining thermal images of the Space Shuttle orbiter during reentry. The trade study investigated the performance characteristics and operating environment of optical instrumentation that may be deployed during a HYTHIRM data collection mission, and specified contributions to the Point Spread Function. It also investigated the constraints that have to be considered in order to optimize deployment through the use of mission planning tools. These tools simulate the radiance modeling of the vehicle as well as the expected spatial resolution based on the Orbiter trajectory and placement of land based or airborne optical sensors for given Mach numbers. Lastly, this report focused on the tools and methodology that have to be in place for real-time mission planning in order to handle the myriad of variables such as trajectory ground track, weather, and instrumentation availability that may only be known in the hours prior to landing

Constraints on Extrasolar Planet Populations from VLT NACO/SDI and MMT SDI and Direct Adaptive Optics Imaging Surveys: Giant Planets are Rare at Large Separations

We examine the implications for the distribution of extrasolar planets based on the null results from two of the largest direct imaging surveys published to date. Combining the measured contrast curves from 22 of the stars observed with the VLT NACO adaptive optics system by Masciadri et al. (2005), and 48 of the stars observed with the VLT NACO SDI and MMT SDI devices by Biller et al. (2007) (for a total of 60 unique stars; the median star for our survey is a 30 Myr K2 star at 25 pc), we consider what distributions of planet masses and semi-major axes can be ruled out by these data, based on Monte Carlo simulations of planet populations. We can set this upper limit with 95% confidence: the fraction of stars with planets with semi-major axis from 20 to 100 AU, and mass >4 M_Jup, is 20% or less. Also, with a distribution of planet mass of dN/dM ~ M^-1.16 between 0.5-13 M_Jup, we can rule out a power-law distribution for semi-major axis (dN/da ~ a^alpha) with index 0 and upper cut-off of 18 AU, and index -0.5 with an upper cut-off of 48 AU. For the distribution suggested by Cumming et al. (2007), a power-law of index -0.61, we can place an upper limit of 75 AU on the semi-major axis distribution. At the 68% confidence level, these upper limits state that fewer than 8% of stars have a planet of mass >4 M_Jup between 20 and 100 AU, and a power-law distribution for semi-major axis with index 0, -0.5, and -0.61 cannot have giant planets beyond 12, 23, and 29 AU, respectively. In general, we find that even null results from direct imaging surveys are very powerful in constraining the distributions of giant planets (0.5-13 M_Jup) at large separations, but more work needs to be done to close the gap between planets that can be detected by direct imaging, and those to which the radial velocity method is sensitive.Comment: 46 pages, 17 figures, accepted to Ap

Present-day uplift of the western Alps

International audienceCollisional mountain belts grow as a consequence of continental plate convergence and eventuallydisappear under the combined effects of gravitational collapse and erosion. Using a decade ofGPS data, we show that the western Alps are currently characterized by zero horizontal velocityboundary conditions, offering the opportunity to investigate orogen evolution at the time ofcessation of plate convergence. We find no significant horizontal motion within the belt, but GPS andlevelling measurements independently show a regional pattern of uplift reaching ~2.5 mm/yr in thenorthwestern Alps. Unless a low viscosity crustal root under the northwestern Alps locally enhancesthe vertical response to surface unloading, the summed effects of isostatic responses to erosion andglaciation explain at most 60% of the observed uplift rates. Rock-uplift rates corrected from transientglacial isostatic adjustment contributions likely exceed erosion rates in the northwestern Alps. In theabsence of active convergence, the observed surface uplift must result from deep-seated processes

The Social and Political Dimensions of the Ebola Response: Global Inequality, Climate Change, and Infectious Disease

The 2014 Ebola crisis has highlighted public-health vulnerabilities in Liberia, Sierra Leone, and Guinea – countries ravaged by extreme poverty, deforestation and mining-related disruption of livelihoods and ecosystems, and bloody civil wars in the cases of Liberia and Sierra Leone. Ebola’s emergence and impact are grounded in the legacy of colonialism and its creation of enduring inequalities within African nations and globally, via neoliberalism and the Washington Consensus. Recent experiences with new and emerging diseases such as SARS and various strains of HN influenzas have demonstrated the effectiveness of a coordinated local and global public health and education-oriented response to contain epidemics. To what extent is international assistance to fight Ebola strengthening local public health and medical capacity in a sustainable way, so that other emerging disease threats, which are accelerating with climate change, may be met successfully? This chapter considers the wide-ranging socio-political, medical, legal and environmental factors that have contributed to the rapid spread of Ebola, with particular emphasis on the politics of the global and public health response and the role of gender, social inequality, colonialism and racism as they relate to the mobilization and establishment of the public health infrastructure required to combat Ebola and other emerging diseases in times of climate change

Nearby low-mass triple system GJ795

We report the results of our optical speckle-interferometric observations of the nearby triple system GJ795 performed with the 6-m BTA telescope with diffraction-limited angular resolution. The three components of the system were optically resolved for the first time. Position measurements allowed us to determine the elements of the inner orbit of the triple system. We use the measured magnitude differences to estimate the absolute magnitudes and spectral types of the components of the triple: $M_{V}^{Aa}$=7.31$\pm$0.08, $M_{V}^{Ab}$=8.66$\pm$0.10, $M_{V}^{B}$=8.42$\pm$0.10, $Sp_{Aa}$ $\approx$K5, $Sp_{Ab}$ $\approx$K9, $Sp_{B}$ $\approx$K8. The total mass of the system is equal to $\Sigma\mathcal{M}_{AB}$=1.69$\pm0.27\mathcal{M}_{\odot}$. We show GJ795 to be a hierarchical triple system which satisfies the empirical stability criteria.Comment: 6 pages, 2 figures, published in Astrophysical Bulleti

Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection

Zaïre ebolavirus (ZEBOV) infection rapidly outruns the host's immunity and leads to death within a week. Fatal cases have been associated with an aberrant innate, proinflammatory immune response followed by a suppressed adaptive response leading to the rapid depletion of peripheral NK cells and lymphocytes. A critical role for NK cells has been suggested but not elucidated. In this genetic study, we investigated the association of KIR genotype with disease outcome by comparing genotypes of a Gabonese control population, IgG+ contacts, survivors, and fatalities of ZEBOV infection. We showed that the activating KIR2DS1 and KIR2DS3 genes associate with fatal outcome in Ebola virus infection. In addition, this study brings supplemental evidence in favor of the specificity of the IgG+ contact population. The outcome of fulminating Ebola virus infection could depend in part on the host's inherited KIR gene repertoire. This supports a key role for KIRs in disease susceptibility to infections

Design and analysis of low boom concepts at Langley Research Center

The objective of the sonic boom research in the current High Speed Research Program is to ultimately make possible overland supersonic flight by a high speed civil transport. To accomplish this objective, it is felt that results in four areas must demonstrate that such a vehicle would be acceptable by the general public, by the airframers, and by the airlines. It should be demonstrated: (1) that some waveform shape has the possibility of being acceptable to the general public; (2) that the atmosphere would not totally destroy such a waveform during propagation; (3) that a viable airplane could be built which produces such a waveform; and (4) that any performance penalty suffered by a low boom aircraft would be counteracted by the economic benefit of overland supersonic flight. The work being done at LaRC is in support of the third element listed above--the area of configuration design. The initial part of the paper will give a review of the theory being used for configuration designs and discuss two theory validation models which were built and tested within the past two years. Discussion of the wind tunnel and theoretical results (linear theory and higher order methods) and their implications for future designs will be included