Elliptical galaxies: fundamental relations, environmental effects and peculiar motions

This thesis investigates the reliability of the D - σ and D - Mg(_2) distance indicators for elliptical galaxies. In particular, we test whether these empirical correlations are affected by differences in the stellar populations of elliptical galaxies associated with their environment. Our final goal is to assess the reality of the large peculiar velocities measured in the local universe as derived using these relations. Our galaxy sample includes ellipticals located in high and low galaxian density regions. The cluster sample is mainly based on new observations of ellipticals in Coma, Abell 2199 and Abell 2634, while the field sample is selected from the literature. For each galaxy we list measurements of the effective radius, effective surface brightness, photometric diameter, velocity dispersion and magnesium index. We first develop a phenomenological framework of galaxy properties that describes all empirical correlations for spheroidal systems, including both giant and dwarf ellipticals. Despite the wide variety of observed correlations, we show that only three provide independent information on the overall structure and metal abundamce of these systems. These three 'fundamental relations' can be expressed in terms of physical variables assuming that both the galaxy mass-to-light ratio (M/L) and the ratio between the effective radii of the dark and luminous matter distributions (R/R(_e)) depend on the mass of the galaxy. The structure of elliptical galaxies is then determined by both the virial theorem and aa intrinsic mass-radius relation. The metallicity of their stellar populations in turn is a function of the galaxy velocity dispersion alone. We compare this framework with a theoretical scenario of galaxy formation that combines the hierarchical clustering and the galactic wind models. This picture provides a consistent explanation of the fundamental relations of all elliptical galaxies assuming R/R(_e) ~ constant for dwarf ellipticals while, for giant ellipticals, we find that R/R(_e) must be a decreasing function of galaxy mass. Our framework strongly suggests that this dependence of R/Re on galaxy mass is the only difference between the two galaxy families. We then study the effect of the environment on the D - σ and D - Mg(_2) distance indicators by comparing ellipticals that reside in the core of the Coma cluster with those in the cluster halo. By studying the variations within one cluster, we avoid the difficulty of decoupling effects induced by distance errors from those due to real environmental differences. We find that ellipticals located in the outer, low-density areas of the Coma cluster have D diameters that are, on average at a given σ or Mg(_2), 10% or 30% larger than their counterparts in the cluster core. Using galaxy evolution models we demonstrate that this effect is consistent with the presence of an intermediate age stellar component in some halo ellipticals. We use the framework of galaxy properties in combination with galaxy evolution models to design a new age-independent distance indicator for ellipticals. This relation allows distances to be estimated with an uncertainty of ~20% and is independent of age/environmental effects. We also offer a simple explanation of the trends observed in the D - σ versus D -Mg(_2) residuals plot. Finally, we use our new distance indicator to readdress previous measurements of peculiar velocities in both the cluster and field environments. For Abell 2199 and Abell 2634 ellipticals, we show that the new distance estimates are in good agreement with those derived using the D - σ and D - Mg(_2) relations. Both clusters are found to have peculiar velocities which are not significantly different from zero. However, when the new distance indicator is applied to field ellipticals we find that the age/environmental effect translates into a spurious positive component of the local peculiar velocity field as derived from D - σ and D - Mg(_2). This effect may provide a simple explanation of the large positive peculiar motions observed towards the Great Attractor

Maintenance therapy with vinflunine plus best supportive care versus best supportive care alone in patients with advanced urothelial carcinoma with a response after first-line chemotherapy (MAJA; SOGUG 2011/02): a multicentre, randomised, controlled, open-label, phase 2 trial.

Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four). Patients were randomly assigned (1:1) to receive vinflunine or best supportive care until disease progression. We initially used block randomisation with a block size of six. Four lists were created for the two stratification factors of starting dose of vinflunine and presence of liver metastases. After a protocol amendment, number of cisplatin and gemcitabine cycles was added as a stratification factor, and eight lists were created, still with a block size of six. Finally, we changed to a minimisation procedure to reduce the risk of imbalance between groups. Vinflunine was given every 21 days as a 20 min intravenous infusion at 320 mg/m2 or at 280 mg/m2 in patients with an Eastern Cooperative Oncology Group performance status score of 1, age 75 years or older, previous pelvic radiotherapy, or creatinine clearance lower than 60 mL/min. The primary endpoint was median progression-free survival longer than 5·3 months in the vinflunine group, assessed by modified intention to treat. Comparison of progression-free survival between treatment groups was a secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01529411. Between April 12, 2012, and Jan 29, 2015, we enrolled 88 patients, of whom 45 were assigned to receive vinflunine and 43 to receive best supportive care. One patient from the vinflunine group was lost to follow-up immediately after randomisation and was excluded from the analyses. One patient in the best supportive care group became ineligible for the study and did not receive treatment due to a delay in enrolment, but was included in the intention-to-treat efficacy analysis. After a median follow-up of 15·6 months (IQR 8·5-26·0), 29 (66%) of 44 patients in the vinflunine group had disease progression and 24 (55%) had died, compared with 36 (84%) of 43 patients with disease progression and 32 (74%) deaths in the best supportive care group. Median progression-free survival was 6·5 months (95% CI 2·0-11·1) in the vinflunine group and 4·2 months (2·1-6·3) in the best supportive care group (hazard ratio 0·59, 95% CI 0·37-0·96, p=0·031). The most common grade 3 or 4 adverse events were neutropenia (eight [18%] of 44 in the vinflunine group vs none of 42 in the best supportive care group), asthenia or fatigue (seven [16%] vs one [2%]), and constipation (six [14%] vs none). 18 serious adverse events were reported in the vinflunine group and 14 in the best supportive care group. One patient in the vinflunine group died from pneumonia that was deemed to be treatment related. In patients with disease control after first-line chemotherapy, progression-free survival exceeded the acceptable threshold with vinflunine maintenance therapy. Moreover, progression-free survival was longer with vinflunine maintenance therapy than with best supportive care. Vinflunine maintenance had an acceptable safety profile. Further studies of the role of vinflunine are warranted. Pierre-Fabre Médicament