A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective

International audienceOBJECTIVES: Adjuvant chemotherapy with vinorelbine plus cisplatin (VC) improves survival in resected non-small-cell lung cancer (NSCLC), but has negative impact on quality of life (QoL). In advanced NSCLC, gemcitabine plus cisplatin (GC) and docetaxel plus cisplatin (DC) exhibit comparable efficacy, with possibly superior QoL compared to VC. This trial investigated these regimens in the adjuvant setting. METHODS: Patients with Stage IB to III NSCLC were eligible following standardized surgery. Overall, 136 patients were included, with 67 and 69 assigned to the GC and DC arms, respectively. Cisplatin (75 mg/m(2), Day [D] 1) plus gemcitabine (1250 mg/m(2), D1 and D8) or docetaxel (75 mg/m(2) D1) were administered for three cycles. Primary end-point was QoL (EORTC QLQ-C30), with the study designed to detect a 10-point difference between arms. Overall survival, safety and cost were secondary end-points. RESULTS: No between-group imbalance was observed in terms of patient characteristics. At inclusion, global health status (GHS) scores (/100) were 63.5 and 62.7 in GC and DC, respectively (P = 0.8), improving to 64.5 and 65.4 after 3 months (P = 0.8). No significant difference in functional or symptoms scores was observed between the arms except for alopecia. Grade 3/4 haematological and non-haematological toxicities were found in 33.8 and 21.7% (P = 0.11), and 33.8 and 26.1% (P = 0.33) of patients, in GC and DC, respectively. At 2 years, 92.9 and 89.8% of patients remained alive in GC and DC, respectively (P = 0.88). CONCLUSIONS: DC and GC adjuvant chemotherapies for completely resected NSCLC were well tolerated and appear free of major QoL effects, and are therefore representing candidates for comparison with the standard VC regimen

Major mergers going Notts: challenges for modern halo finders

Merging haloes with similar masses (i.e. major mergers) pose significant challenges for halo finders. We compare five halo-finding algorithms’ (ahf, hbt, rockstar, subfind, and velociraptor) recovery of halo properties for both isolated and cosmological major mergers. We find that halo positions and velocities are often robust, but mass biases exist for every technique. The algorithms also show strong disagreement in the prevalence and duration of major mergers, especially at high redshifts (z > 1). This raises significant uncertainties for theoretical models that require major mergers for, e.g. galaxy morphology changes, size changes, or black hole growth, as well as for finding Bullet Cluster analogues. All finders not using temporal information also show host halo and subhalo relationship swaps over successive timesteps, requiring careful merger tree construction to avoid problematic mass accretion histories. We suggest that future algorithms should combine phase-space and temporal information to avoid the issues presented

Subhaloes gone Notts: the clustering properties of subhaloes

We present a study of the substructure finder dependence of subhalo clustering in the Aquarius Simulation. We run 11 different subhalo finders on the haloes of the Aquarius Simulation and study their differences in the density profile, mass fraction and two-point correlation function of subhaloes in haloes. We also study the mass and vmax dependence of subhalo clustering. As the Aquarius Simulation has been run at different resolutions, we study the convergence with higher resolutions. We find that the agreement between finders is at around the 10 per cent level inside R200 and at intermediate resolutions when a mass threshold is applied, and better than 5 per cent when vmax is restricted instead of mass. However, some discrepancies appear in the highest resolution, underlined by an observed resolution dependence of subhalo clustering. This dependence is stronger for the smallest subhaloes, which are more clustered in the highest resolution, due to the detection of subhaloes within subhaloes (the sub-subhalo term). This effect modifies the mass dependence of clustering in the highest resolutions. We discuss implications of our results for models of subhalo clustering and their relation with galaxy clustering

Nitrogen Isotopic Composition and Density of the Archean Atmosphere

Understanding the atmosphere's composition during the Archean eon is a fundamental issue to unravel ancient environmental conditions. We show from the analysis of nitrogen and argon isotopes in fluid inclusions trapped in 3.0-3.5 Ga hydrothermal quartz that the PN2 of the Archean atmosphere was lower than 1.1 bar, possibly as low as 0.5 bar, and had a nitrogen isotopic composition comparable to the present-day one. These results imply that dinitrogen did not play a significant role in the thermal budget of the ancient Earth and that the Archean PCO2 was probably lower than 0.7 bar

Planarias terrestres exóticas en Torrevieja (Alicante): presencia de Bipalium cf. kewense Mosely, 1878 (Platyhelminthes, Tricladida, Geoplanidae)

The non-indigenous terrestrial flatworm Bipalium cf. kewense Moseley, 1878 is reported in Alicante province (Iberian Peninsula) for the first time. This occurrence is the most meridional from the Comunidad Valenciana, enlarging its distribution in this area. As the species is considered an invasive alien species in this region, the potential risk of colonizing natural environments closer to the observation area is evaluated.Se cita por primera vez en la provincia de Alicante (península ibérica) la especie de planaria terrestre exótica Bipalium cf. kewense Moseley, 1878. Con esta presencia aumenta el área de distribución de la especie en la Comunidad Valenciana, siendo la más meridional. Dado que la especie está considerada en esta comunidad autónoma como especie exótica invasora, se valora el riesgo potencial de colonización de ambientes naturales limítrofes a la zona de observación (jardín privado en zona urbanizada

Cosmic CARNage I: on the calibration of galaxy formation models

We present a comparison of nine galaxy formation models, eight semi-analytical, and one halo occupation distribution model, run on the same underlying cold dark matter simulation (cosmological box of comoving width 125h−1 Mpc, with a dark-matter particle mass of 1.24 × 109h−1M) and the same merger trees. While their free parameters have been calibrated to the same observational data sets using two approaches, they nevertheless retain some ‘memory’ of any previous calibration that served as the starting point (especially for the manually tuned models). For the first calibration, models reproduce the observed z = 0 galaxy stellar mass function (SMF) within 3σ. The second calibration extended the observational data to include the z = 2 SMF alongside the z ∼ 0 star formation rate function, cold gas mass, and the black hole–bulge mass relation. Encapsulating the observed evolution of the SMF from z = 2 to 0 is found to be very hard within the context of the physics currently included in the models. We finally use our calibrated models to study the evolution of the stellar-to-halo mass (SHM) ratio. For all models, we find that the peak value of the SHM relation decreases with redshift. However, the trends seen for the evolution of the peak position as well as the mean scatter in the SHM relation are rather weak and strongly model dependent. Both the calibration data sets and model results are publicly available

A note on comonotonicity and positivity of the control components of decoupled quadratic FBSDE

In this small note we are concerned with the solution of Forward-Backward Stochastic Differential Equations (FBSDE) with drivers that grow quadratically in the control component (quadratic growth FBSDE or qgFBSDE). The main theorem is a comparison result that allows comparing componentwise the signs of the control processes of two different qgFBSDE. As a byproduct one obtains conditions that allow establishing the positivity of the control process.Comment: accepted for publicatio

Letrozole sensitizes breast cancer cells to ionizing radiation

INTRODUCTION: Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer. Letrozole, an aromatase inhibitor, is being evaluated in the adjuvant setting. We determined the effects of the combination of RT and letrozole in the aromatase-expressing breast tumour cell line MCF-7CA, stably transfected with the CYP19 gene. METHODS: Irradiations were performed using a cobalt-60 source with doses ranging from 0 to 4 Gy. Cells were incubated with androstenedione in the presence or absence of letrozole. Effects of treatment were evaluated using clonogenic assays, tetrazolium salt colorimetric (MTT) assays, and cell number determinations. Cell-cycle analyses were conducted using flow cytometry. RESULTS: The survival fraction at 2 Gy was 0.66 for RT alone and was 0.44 for RT plus letrozole (P = 0.02). Growth of MCF-7CA cells as measured by the cell number 6 days after radiotherapy (2 and 4 Gy) was decreased by 76% in those cells treated additionally with letrozole (0.7 μM) compared with those receiving radiotherapy alone (P = 0.009). Growth inhibition, assessed either by cell number (P = 0.009) or by the MTT assay (P = 0.02), was increased after 12 days of the combination treatment. Compared with radiation alone, the combination of radiation and letrozole produced a significant decrease in radiation-induced G(2 )phase arrest and a decrease of cells in the S phase, with cell redistribution in the G(1 )phase. CONCLUSIONS: These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer

Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers

Purpose To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Methods Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up. Results Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC d