CN abundance variations on the main sequence of 47 Tuc

We report on a deep spectroscopic survey for star-to-star CN variations along the main sequence (MS) of the globular cluster 47 Tuc with ESO's VLT. We find a significant bimodal distribution in the S(3839) index for main-sequence stars in the mass range of ~0.85 to 0.65 M_sun, or from the main-sequence turn-off down to ~2.5 mag below the main sequence turn-off. An anti-correlation of CN and CH is evident on the MS. The result is discussed in the context of the ability of faint MS stars to alter their surface composition through internal evolutionary effects. We argue against internal stellar evolution as the only origin for the abundance spread in 47 Tuc; an external origin such as pollution seems to be more likely.Comment: 29 pages, including 8 figures; Accepted for publication in AJ, scheduled for Januar

Draco -- A Failure of the Tidal Model

We test whether the structural properties of the nearby dwarf spheroidal (dSph) galaxy Draco, a well-studied Milky Way companion, can be reconciled with the suggestion that dSphs are unbound tidal remnants with a large depth extent along the line of sight. In order to apply the observational test of this hypothesis suggested by Klessen & Zhao, we use public photometric data from the Sloan Digital Sky Survey (SDSS) to explore the width of Draco's blue horizontal branch over a range of areas covering 0.06 square degrees to 6.25 square degrees centered on Draco. The SDSS database is the only currently existing database with sufficient depth and area coverage to permit a stringent test of the tidal models. We show that blue horizontal branch stars extend beyond the previously inferred limiting radii of Draco, consistent with the observed absence of a truncated stellar surface density profile of this dSph. We calculate new models for a galaxy without dark matter, using Draco's morphological properties as constraints. The resulting models are unable to reproduce the narrow observed horizontal branch width of Draco, which stays roughly constant regardless of the field of view. We conclude that Draco cannot be the remnant of a tidally disrupted satellite, but is probably strongly dark-matter dominated. (ABSTRACT ABBREVIATED)Comment: 26 pages, 9 figures included, accepted for publication in ApJ, high-resolution version available at http://www.aip.de./~ralf/Publications/p22.abstract.htm

Genomic Profiling in Luminal Breast Cancer

The developments in gene expression analysis have made it possible tosub-classify hormone receptor-positive (luminal) breast cancer indifferent prognostic subgroups. This sub-classification is currentlyused in clinical routine as prognostic signature (e. g. 21-gene OnoctypeDX (R), 70-gene Mammaprint (R)). As yet, the optimal method forsub-classification has not been defined. Moreover, there is no evidencefrom prospective trials. This review explores widely used genomicsignatures in luminal breast cancer, making a critical appraisal ofevidence from retrospective/prospective trials. It is based onsystematic literature search performed using Medline (accessed September2013) and abstracts presented at the Annual Meeting of American Societyof Clinical Oncology and San Antonio Breast Cancer Symposium

WSG ADAPT - adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer: study protocol for a prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III trial

Background: Adjuvant treatment decision-making based on conventional clinical/pathological and prognostic single molecular markers or genomic signatures is a therapeutic area in which over-/under-treatment are still key clinical problems even though substantial and continuous improvement of outcome has been achieved over the past decades. Response to therapy is currently not considered in the decision-making procedure. ADAPT is one of the first new generation (neo) adjuvant trials dealing with individualization of (neo) adjuvant decision-making in early breast cancer and aims to establish early predictive surrogate markers, e. g., Ki-67, for therapy response under a short induction treatment in order to maximally individualize therapy and avoid unnecessary toxicity by ineffective treatment. Methods/design: The prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III ADAPT trial has an innovative ``umbrella{''} protocol design. The ``umbrella{''} is common for all patients, consisting of dynamic testing of early therapy response. ADAPT will recruit 4,936 patients according to their respective breast cancer subtype in four distinct sub-trials at 80 trial sites in Germany; 4,000 patients with hormone receptor positive (HR+) and HER2 negative disease will be included in the ADAPT HR+/HER2-sub-trial, where treatment decision is based on risk assessment and therapy response to induction therapy, and 380 patients will be included in ADAPT HER2+/HR+. A further 220 patients will be included in ADAPT HER2+/HR- and 336 patients will be recruited for ADAPT Triple Negative. These three sub-trials focus on identification of early surrogate markers for therapy success in the neoadjuvant setting. Patients will be allocated to the respective sub-trial according to the result of their diagnostic core biopsy, as reported by local/central pathology for HR and HER2 status. Discussion: Recent trials, such as the GeparTrio, have shown that response-guided therapy using clinical response may improve outcome. For chemotherapy or HER2-targeted treatment, pathologic complete response in a neoadjuvant setting is an excellent predictor of outcome. For endocrine therapy, response to short induction treatment - as defined by decrease in tumor cell proliferation - strongly correlates with outcome. ADAPT now aims to combine static prognostic and dynamic predictive markers, focusing not just on single therapeutic targets, but also on general markers of proliferation and cell death. Biomarker analysis will help to optimize selection of subtype-specific treatment. Trial registration: ClinicalTrials.gov: ADAPT Umbrella: NCT01781338; ADAPT HR+/HER2-: NCT01779206; ADAPT HER2+/HR+: NCT01745965; ADAPT HER2+/HR-: NCT01817452; ADAPT TN: NCT01815242

Population Gradients in Local Group Dwarf Spheroidals

We present a systematic and homogeneous analysis of population gradients for the Local Group dwarf spheroidals (dSphs) Carina, Sculptor, Sextans, Tucana, Andromeda I-III, V, and VI. For all of the Milky Way companions studied here we find significant population gradients. The same is true for the remote dSph Tucana located at the outskirts of the LG. Among the M 31 dSph companions only Andromeda I and VI show obvious gradients. In all cases where a HB morphology gradient is visible, the red HB stars are more centrally concentrated. The occurence of a HB morphological gradient shows a correlation with a morphology gradient in the red giant branch. It seems likely that metallicity is the driver of the gradients in Sextans, Sculptor, Tucana, and Andromeda VI, while age is an important factor in Carina. We find no evidence that the vicinity of a nearby massive spiral galaxy influences the formation of the population gradients.Comment: accepted for publication in AJ; 25 pages; 11 images in jpeg and png forma