Repeated nipple fluid aspiration

Background: Despite intensive surveillance, a high rate of interval malignancies is still seen in women at increased breast cancer risk. Therefore, novel screening modalities aiming at early detection remain needed. The intraductal approach offers the possibility to directly sample fluid containing cells, DNA and proteins from the mammary ductal system where, in the majority of cases, breast cancer originates. Fluid from the breast can non-invasively be obtained by oxytocin-assisted vacuum aspiration, called nipple fluid aspiration (NFA). The goal of this feasibility study was to evaluate the potential of repeated NFA, which is a critical and essential step to evaluate its possible value as a breast cancer screening method. Methods: In this multicenter, prospective study, we annually collected nipple fluid for up to 5 consecutive years from women at increased breast cancer risk, and performed a questionnaire-based survey regarding discomfort of the aspiration. Endpoints of the current interim analyses were the feasibility and results of 994 NFA procedures in 451 women with total follow-up of 560 person years of observation. Results: In this large group of women at increased risk of breast cancer, repetitive NFA appeared to be feasible and safe. In 66.4% of aspirated breasts, nipple fluid was successfully obtained. Independent predictive factors for successful NFA were premenopausal status, spontaneous nipple discharge, smaller breast size, bilateral oophorectomy and previous use of hormone replacement therapy or anti-hormonal treatment. The procedure was well tolerated with low discomfort. Drop-out rate was 20%, which was mainly due to repeated unsuccessful aspiration attempts. Only 1.6% of women prematurely declined further participation because of side effects. Conclusions: Repeated NFA in women at increased breast cancer risk is feasible and safe. Therefore, NFA is a promising method to non-invasively obtain a valuable source of potential breast cancer specific biomarkers

Scale-free static and dynamical correlations in melts of monodisperse and Flory-distributed homopolymers: A review of recent bond-fluctuation model studies

It has been assumed until very recently that all long-range correlations are screened in three-dimensional melts of linear homopolymers on distances beyond the correlation length $\xi$ characterizing the decay of the density fluctuations. Summarizing simulation results obtained by means of a variant of the bond-fluctuation model with finite monomer excluded volume interactions and topology violating local and global Monte Carlo moves, we show that due to an interplay of the chain connectivity and the incompressibility constraint, both static and dynamical correlations arise on distances $r \gg \xi$. These correlations are scale-free and, surprisingly, do not depend explicitly on the compressibility of the solution. Both monodisperse and (essentially) Flory-distributed equilibrium polymers are considered.Comment: 60 pages, 49 figure

Canonical Wnt signaling negatively modulates regulatory T cell function

Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that Tcell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes. The activation of Wnt signaling reduced Treg-mediated suppression both invitro and invivo, whereas disruption of Wnt signaling in Treg cells enhanced their suppressive capacity. The activation of effector Tcells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced under inflammatory conditions represses Treg cell function, allowing a productive immune response, but, if uncontrolled, could lead to the development of autoimmunity

Multi-wavelength studies of GRB afterglows

We present the discovery of SN 1998bw in the error box of GRB 980425. Our discovery raises the possibility that very different mechanisms may give rise to GRBs, which differ little in their gamma-ray properties. We also present multi-wavelength observations of several gamma-ray burst afterglows: (i) the optical light curves of GRB 970228, GRB 970508, GRB 980326, and GRB 980703 (ii) the GRB 970508 radio 1.4 GHz and mm (86 GHz) lightcurves, and (iii) the X-ray to radio spectrum of GRB 970508 on May 21 (12.1 days after trigger). A successful and consistent description of afterglow observations is given by a blast wave model, in which a significant fraction of the electrons cool rapidly. For GRB 970508 it succesfully describes the observations ranging in time from trigger until several months later, over 9 decades in frequency from radio to X rays

3MeerLICHT and BlackGEM: custom-built telescopes to detect faint optical transients

We present the MeerLICHT and BlackGEM telescopes, which are wide-field optical telescopes that are currently being built to study transient phenomena, gravitational wave counterparts and variable stars. The telescopes have 65 cm primary mirrors and a 2.7 square degree field-of-view. The MeerLICHT and BlackGEM projects have different science goals, but will use identical telescopes. The first telescope, MeerLICHT, will be commissioned at Sutherland (South Africa) in the first quarter of 2017. It will co-point with MeerKAT to collect optical data commensurate with the radio observations. After careful analysis of MeerLICHT's performance, three telescopes of the same type will be commissioned in La Silla (Chile) in 2018 to form phase I of the BlackGEM array. BlackGEM aims at detecting and characterizing optical counterparts of gravitational wave events detected by Advanced LIGO and Virgo. In this contribution we present an overview of the science goals, the design and the status of the two projects