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PBC J2333.9-2343 is a giant radio galaxy at z = 0.047 with a bright central core associated to a blazar nucleus. If the nuclear blazar jet is a new phase of the jet activity, then the small orientation angle suggest a dramatic change of the jet direction. We present observations obtained between September 2018 and January 2019 (cadence larger than three days) with Effeslberg, SMARTS-1.3m, ZTF, ATLAS, Swift, and Fermi-LAT, and between April-July 2019 (daily cadence) with SMARTS-1.3m and ATLAS. Large (>2x) flux increases are observed on timescales shorter than a month, which are interpreted as flaring events. The cross correlation between the SMARTS-1.3m monitoring in the NIR and optical shows that these data do not show significant time lag within the measured errors. A comparison of the optical variability properties between non-blazars and blazars AGN shows that PBC J2333.9-2343 has properties more comparable to the latter. The SED of the nucleus shows two peaks, that were fitted with a one zone leptonic model. Our data and modelling shows that the high energy peak is dominated by External Compton from the dusty torus with mild contribution from Inverse Compton from the jet. The derived jet angle of 3 degrees is also typical of a blazar. Therefore, we confirm the presence of a blazar-like core in the center of this giant radio galaxy, likely a Flat Spectrum Radio Quasar with peculiar properties., Accepted for publication in MNRAS. 15 pages, 6 figures, 2 appendix including tables and figures

Introduction: In the spring of 2020, coronavirus disease 2019 posed a substantial challenge for countries and their healthcare systems. In Germany, over 70% of all cancer patients are treated in an outpatient setting, so gynecologic oncology practices are the guarantors of optimal patient care. We developed a survey to evaluate the management of gynecologic oncology patients. Methods: The survey consisted of 38 questions and was sent to the members of the Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V. (BNGO), a professional association of gynecologic oncologists in the outpatient sector in Germany. Results: The survey was completed by 54 out of 133 (41%) gynecologic oncologists from 14 out of 15 (93%) federal states where the BNGO is represented. Facing the pandemic, popular measures were mask requirements (100%), restriction of access to practices (94%), increased number of disinfectant dispensers (85%), installment of panes of acrylic glass (76%), or spatial alterations (67%). For most patients the pandemic had no influence on prioritization of therapies (82%) or prescribed systemic treatments (87%). Despite an increase in perceived psychological burden among the staff (72%), 85% (45/54) of the practices were not offered any additional psychological support. Discussion and Conclusion: As most cancer patients in Germany are treated in an outpatient setting, a suitable reaction of oncology centers to the new circumstances was crucial to secure optimal treatment and patient care. Nevertheless, the low prioritization of mental health or distress of healthcare workers poses a serious threat to the maintenance of optimal medical care in further waves of the pandemic.

1% of all breast cancer cases occur in men. There are significant differences regarding clinical behaviour and genetic profiles between female (FBC) and male breast cancer (MBC). Parameters for decision-making on treatment and prognosis are derived from FBC. Ki67 has a high value as a prognostic and predictive factor in FBC, but accurate Ki67 cut-off points for MBC are missing. In this study, we aimed to evaluate adequate examination methods and reliable cut-off points for Ki67 to assess the highest prognostic value for patient’s overall survival (OS). In this multicentric retrospective study, histological specimens were obtained from 104 male patients who were diagnosed and treated for primary invasive breast cancer. We applied three methods of Ki67 analysis: Tumor average scoring (TA), tumor border scoring (TB) and hot-spot scoring (HS). Calculated Ki67 cut-off points for each method were assessed as a threshold for patients’ overall survival (OS). Ki67 cut-off points were 13.5 for the TA group, 22.5 for the HS group and 17.5 for the TB group. Only Ki67 TA cut-off calculations demonstrated statistical significance (p = 0.04). Ki67 expression analysis of TA showed that more than 90% of patients with low Ki67 levels (

Linking supernovae to their progenitors is a powerful method for furthering our understanding of the physical origin of their observed differences, while at the same time testing stellar evolution theory. In this second study of a series of three papers where we characterise SNe II to understand their diversity, we derive progenitor properties (initial and ejecta masses, and radius), explosion energy, $^{56}$Ni mass, and its degree of mixing within the ejecta for a large sample of SNe II. This dataset was obtained by the Carnegie Supernova Project-I and is characterised by a high cadence of their optical and NIR light curves and optical spectra that were homogeneously observed and processed. A large grid of hydrodynamical models and a fitting procedure based on MCMC methods were used to fit the bolometric light curve and the evolution of the photospheric velocity of 53 SNe II. We infer ejecta masses between 7.9 and 14.8 $M_{\odot}$, explosion energies between 0.15 and 1.40 foe, and $^{56}$Ni masses between 0.006 and 0.069 $M_{\odot}$. We define a subset of 24~SNe (the `gold sample') with well-sampled bolometric light curves and expansion velocities for which we consider the results more robust. Most SNe~II in the gold sample ($\sim$88%) are found with ejecta masses in the range of $\sim$8-10 $M_{\odot}$, coming from low zero-age main-sequence masses (9-12 $M_{\odot}$). The modelling of the initial-mass distribution of the gold sample gives an upper mass limit of 21.3$^{+3.8}_{-0.4}$ $M_{\odot}$ and a much steeper distribution than that for a Salpeter massive-star IMF. This IMF incompatibility is due to the large number of low-mass progenitors found -- when assuming standard stellar evolution. This may imply that high-mass progenitors lose more mass during their lives than predicted. However, a deeper analysis of all stellar evolution assumptions is required to test this hypothesis., Comment: Accepted for publication in Astronomy & Astrophysics

ZusammenfassungVom 14. bis 16. November 2019 fand in Lissabon die fünfte internationale Konsensuskonferenz ABC5 (Advanced Breast Cancer Fifth Consensus) zu Diagnostik und Behandlung des fortgeschrittenen Mammakarzinoms statt. Ziel ist es, die Behandlung der Patientinnen mit fortgeschrittenem Mammakarzinom weltweit auf evidenzbasierter Grundlage zu standardisieren und sicherzustellen, dass Patientinnen überall auf der Welt adäquat behandelt werden und Zugang zu neuen Therapien erhalten. Ein inhaltlicher Schwerpunkt lag dieses Jahr auf neuen Entwicklungen und Studienergebnissen beim fortgeschrittenen Mammakarzinom sowie der Präzisionsmedizin. Zudem ist die Zusammenarbeit mit den Patientenvertreterinnen aus aller Welt ein wichtiges Anliegen der ABC-Konferenz, weshalb in dem international zusammengesetzten ABC-Panel auch Patientenvertreterinnen sind. Im vorliegenden Manuskript werden die Abstimmungsergebnisse der ABC5-Panelisten vor Ort durch eine Arbeitsgruppe deutscher Brustkrebsexperten für den Therapiealltag in Deutschland kommentiert. Der Kommentierung liegen die Empfehlungen der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), Kommission „Mamma“, zugrunde. Sie erscheint sinnvoll, da in den ABC-Konsensus auch länderspezifische Besonderheiten einfließen.

The Advanced Breast Cancer Fifth International Consensus Conference (ABC5) which focuses on the diagnosis and treatment of advanced breast cancer was held in Lisbon on November 14 – 16, 2019. The aim of the conference is to standardize the treatment of advanced breast cancer worldwide using evidence-based data and to ensure that patients with advanced breast disease anywhere in the world are treated appropriately and have access to the latest therapies. This year, the emphasis was on new developments and study results from patients with advanced breast cancer as well as precision medicine. The collaboration with patient advocates from all over the globe is also an important goal of the ABC Conference, which is why the international ABC panel also included a number of patient advocates. We present a commentary on the voting results of the ABC5 panelists in Lisbon by a working group of German breast cancer specialists together with the implications for routine clinical care in Germany. The commentary is based on the recommendations of the Breast Commission of the German Gynecological Oncology Working Group (AGO). This commentary is useful, it includes country-specific features for the ABC consensus.

We present multi-wavelength time-series spectroscopy of SN 2013aa and SN 2017cbv, two Type Ia supernovae (SNe Ia) on the outskirts of the same host galaxy, NGC 5643. This work utilizes new nebular-phase near-infrared (NIR) spectra obtained by the Carnegie Supernova Project-II, in addition to previously published optical and NIR spectra. By measuring nebular-phase [Fe II] lines in both the optical and NIR, we examine the explosion kinematics and test the efficacy of several emission line fitting techniques commonly used in the literature. The NIR [Fe II] 1.644 $\mu$m line provides the most robust velocity measurements against variations due to the choice of the fit method and line blending. The resulting effects on velocity measurements due to choosing different fit methods, initial fit parameters, continuum and line profile functions, and fit region boundaries were also investigated. The NIR [Fe II] velocities yield the same radial shift direction as velocities measured using the optical [Fe II] 7155 A line, but the sizes of the shifts are consistently and substantially lower, pointing to a potential issue in optical studies. The NIR [Fe II] 1.644 $\mu$m emission profile shows a lack of significant asymmetry in both SNe Ia, and the observed low velocities elevate the importance for correcting for any radial velocity contribution from the host galaxy's rotation. The low [Fe II] velocities measured in the NIR at nebular phases disfavors most progenitor scenarios in close double-degenerate systems for both SN 2013aa and SN 2017cbv. The time evolution of the NIR [Fe II] 1.644 $\mu$m line also indicates moderately high progenitor white dwarf central density and potentially high magnetic fields. These sibling SNe Ia were well observed at both early and late times, providing an excellent opportunity to study the intrinsic diversity of SNe Ia., Comment: submitted to ApJ on Oct 4, 2022 accepted for publication on Dec 19, 2022

Tucker et al., On 2019 August 14 at 21:10:39 UTC, the LIGO/Virgo Collaboration (LVC) detected a possible neutron star–black hole merger (NSBH), the first ever identified. An extensive search for an optical counterpart of this event, designated GW190814, was undertaken using the Dark Energy Camera on the 4 m Victor M. Blanco Telescope at the Cerro Tololo Inter-American Observatory. Target of Opportunity interrupts were issued on eight separate nights to observe 11 candidates using the 4.1 m Southern Astrophysical Research (SOAR) telescope's Goodman High Throughput Spectrograph in order to assess whether any of these transients was likely to be an optical counterpart of the possible NSBH merger. Here, we describe the process of observing with SOAR, the analysis of our spectra, our spectroscopic typing methodology, and our resultant conclusion that none of the candidates corresponded to the gravitational wave merger event but were all instead other transients. Finally, we describe the lessons learned from this effort. Application of these lessons will be critical for a successful community spectroscopic follow-up program for LVC observing run 4 (O4) and beyond., Funding for the DES Projects has been provided by the DOE and NSF(USA), MEC/MICINN/MINECO (Spain), STFC (UK), HEFCE(UK). NCSA (UIUC), KICP (U. Chicago), CCAPP (Ohio State), MIFPA (Texas A&M), CNPQ, FAPERJ, FINEP (Brazil), DFG (Germany) and the Collaborating Institutions in the Dark Energy Survey. The DES Data Management System is supported by the NSF under grant Nos. AST-1138766 and AST-1536171. The DES participants from Spanish institutions are partially supported by MINECO under grants AYA2015-71825, ESP2015-88861, FPA2015-68048, and Centro de Excelencia SEV-2016-0588, SEV-2016-0597 and MDM-2015-0509. Research leading to these results has received funding from the ERC under the EU's 7th Framework Programme including grants ERC 240672, 291329 and 306478. I.A. is a CIFAR Azrieli Global Scholar in the Gravity and the Extreme Universe Program and acknowledges support from that program, from the European Research Council (ERC) under the European Unions Horizon 2020 research and innovation program (grant agreement number 852097), from the Israel Science Foundation (grant number 2752/19), from the United States–Israel Binational Science Foundation (BSF), and from the Israeli Council for Higher Education Alon Fellowship.

Background: In the pivotal BOLERO-2 trial, everolimus (EVE) + exemestane (EXE) more than doubled the median progression-free survival (PFS) vs EXE alone in hormone receptor positive (HR+), human epidermal growth factor-receptor 2-negative (HER2-) advanced breast cancer (ABC) recurring/progressing on/after prior non-steroidal aromatase inhibitors (NSAIs). BRAWO is a German non-interventional study conducted in patients (pts) with HR+, HER2–ABC receiving EVE + EXE, according to Summary of Product Characteristics (SmPC), in routine clinical practice. Here we report the final PFS and safety results. Methods: This multicenter study documented 2100 pts between October 2012 and December 2017 across 341 sites in Germany. Postmenopausal women with HR+, HER2– ABC with recurrence or progression after a NSAI were included. Primary observation parameters included the evaluation of the effectiveness of EVE + EXE used in routine care for the entire pt group. Results: In the final analysis, out of the 2100 documented pts, 2074 were included in the full analysis set. The median time since the primary diagnosis was 7.1 years and the median time from first sign of relapse (local recurrence or distant metastases) was 2.1 years. At baseline, 54.1% of pts presented with visceral metastases and 50.1% had an ECOG performance status of 0. Approximately, 63% of pts started with EVE 10 mg (median duration of exposure: 5.1 months; 95% CI, 4.6-5.4), while 34.1% started with EVE 5 mg (median duration of exposure: 4.6 months; 95% CI, 4.1-5.2). The distribution of treatment lines was as follows: first line, 28.7% (n=595); second line, 31.9% (n=662); third line, 18.1% (n=376); fourth line, 10.7% (n=221) and, fifth line and later, 10.6% (n=220). Treatment was discontinued by 55.7% of pts (n=1170) due to progressive disease and 26% of pts (n=546) due to adverse events. The Kaplan-Meier estimate of the median PFS was 6.6 months (95% CI, 6.2-7.0). The best overall responses, based on clinical routine, were complete response, 0.8% (n=17), partial response, 7.4% (n=150), and stable disease, 41.3% (n=842). The general safety profile was consistent with the previously reported safety findings. The most common adverse events were stomatitis (any grade: 42.6%, grade 3: 3.8%, grade 4: Conclusions: Data from BRAWO support EVE + EXE as a suitable treatment option with a reasonable safety profile for HR+, HER2− ABC recurring or progressing on/after prior NSAIs. Citation Format: Lüftner D, Schuetz F, Schneeweiss A, Grischke E-M, Bloch W, Decker T, Uleer C, Salat C, Förster F, Schmidt M, Mundhenke C, Tesch H, Jackisch C, Fischer T, Guderian G, Hanson S, Fasching P. Everolimus + exemestane for HR+ advanced breast cancer in routine clinical practice- Final results from the non-interventional trial, BRAWO [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-08.

The boron-10 based Multi-Grid detector is being developed as an alternative to helium-3 based neutron detectors. At the European Spallation Source, the detector will be used for time-of-flight neutron spectroscopy at cold to thermal neutron energies. The objective of this work is to investigate fine time- and energy-resolved effects of the Multi-Grid detector, down to a few $\mu$eV, while comparing it to the performance of a typical helium-3 tube. Furthermore, it is to characterize differences between the detector technologies in terms of internal scattering, as well as the time reconstruction of ~ $\mu$s short neutron pulses. The data were taken at the Helmholtz Zentrum Berlin, where the Multi-Grid detector and a helium-3 tube were installed at the ESS test beamline, V20. Using a Fermi-chopper, the neutron beam of the reactor was chopped into a few tens of $\mu$s wide pulses before reaching the detector, located a few tens of cm downstream. The data of the measurements show an agreement between the derived and calculated neutron detection efficiency curve. The data also provide fine details on the effect of internal scattering, and how it can be reduced. For the first time, the chopper resolution was comparable to the timing resolution of the Multi-Grid detector. This allowed a detailed study of time- and energy resolved effects, as well as a comparison with a typical helium-3 tube., Comment: 37 pages, 21 figures

The classic classification scheme for Active Galactic Nuclei (AGNs) was recently challenged by the discovery of the so-called changing-state (changing-look) AGNs (CSAGNs). The physical mechanism behind this phenomenon is still a matter of open debate and the samples are too small and of serendipitous nature to provide robust answers. In order to tackle this problem, we need to design methods that are able to detect AGN right in the act of changing-state. Here we present an anomaly detection (AD) technique designed to identify AGN light curves with anomalous behaviors in massive datasets. The main aim of this technique is to identify CSAGN at different stages of the transition, but it can also be used for more general purposes, such as cleaning massive datasets for AGN variability analyses. We used light curves from the Zwicky Transient Facility data release 5 (ZTF DR5), containing a sample of 230,451 AGNs of different classes. The ZTF DR5 light curves were modeled with a Variational Recurrent Autoencoder (VRAE) architecture, that allowed us to obtain a set of attributes from the VRAE latent space that describes the general behaviour of our sample. These attributes were then used as features for an Isolation Forest (IF) algorithm, that is an anomaly detector for a "one class" kind of problem. We used the VRAE reconstruction errors and the IF anomaly score to select a sample of 8,809 anomalies. These anomalies are dominated by bogus candidates, but we were able to identify 75 promising CSAGN candidates., Comment: Accepted for publication in the Astronomical Journal (AJ)

While income inequality in Austria is relatively low compared to many other OECD countries, social mobility lags behind. Socio-economic outcomes carry over strongly from one generation to the next: more than elsewhere, fathers’ earnings are a strong predictor of the earnings of their prime-age children. This reflects strong persistence across generations in occupational and educational outcomes, particularly for women and migrants. Relative income positions also tend to strongly persist over people’s lives, in particular at the top and bottom. Meanwhile, the middle-income group is polarising, with downward risks rising for the lower middle. Longer-term earnings trajectories (over 15 years) display marked gender differences, with women facing weaker chances of moving up and greater risks of sliding down. This paper identifies policies that promote or hamper social mobility in four domains. First, good-quality early childhood education and care can be a catalyst for upward mobility. Participation rates have significantly risen over the last decade, but still lag those in many OECD countries. Further investment is needed to improve quality and status of formal childcare. Second, tackling low educational mobility in Austria requires ensuring a successful school-to-work transition. Austria provides targeted support for those who struggle, but it could improve funding for disadvantaged schools and consider the appropriateness of "tracking" students at such a young age. Third, reducing gender inequality in the labour market would greatly improve social mobility. This requires raising incentives for a more equal sharing of family and work responsibilities in the areas of tax policy, parental leave and family and care benefits. Fourth, the Austrian tax and benefit system provides comparatively adequate protection against income shocks. The high concentration of household wealth, combined with the absence of inheritance taxation, however implies that inequalities of opportunity remain large.

Type II supernovae (SNe II) show great photometric and spectroscopic diversity which is attributed to the varied physical characteristics of their progenitor and explosion properties. In this study, the third of a series of papers where we analyse a large sample of SNe II observed by the Carnegie Supernova Project-I, we present correlations between their observed and physical properties. Our analysis shows that explosion energy is the physical property that correlates with the highest number of parameters. We recover previously suggested relationships between the hydrogen-rich envelope mass and the plateau duration, and find that more luminous SNe II with higher expansion velocities, faster declining light curves, and higher 56Ni masses are consistent with higher energy explosions. In addition, faster declining SNe II (usually called SNe IIL) are also compatible with more concentrated 56Ni in the inner regions of the ejecta. Positive trends are found between the initial mass, explosion energy, and 56Ni mass. While the explosion energy spans the full range explored with our models, the initial mass generally arises from a relatively narrow range. Observable properties were measured from our grid of bolometric LC and photospheric velocity models to determine the effect of each physical parameter on the observed SN II diversity. We argue that explosion energy is the physical parameter causing the greatest impact on SN II diversity, that is, assuming the non-rotating solar-metallicity single-star evolution as in the models used in this study. The inclusion of pre-SN models assuming higher mass loss produces a significant increase in the strength of some correlations, particularly those between the progenitor hydrogen-rich envelope mass and the plateau and optically thick phase durations. These differences clearly show the impact of having different treatments of stellar evolution, implying that changes in the assumption of standard single-star evolution are necessary for a complete understanding of SN II diversity., The work of the Carnegie Supernova Project was supported by the National Science Foundation under grants AST-0306969, AST-0607438, AST-1008343, AST-1613426, AST-1613472, and AST-1613455. L.M. acknowledges support from a CONICET fellowship. L.M. and M.O. acknowledge support from UNRN PI2018 40B885 grant. M.H. acknowledges support from the Hagler Institute of Advanced Study at Texas A&M University. S.G.G. acknowledges support by FCT under Project CRISP PTDC/FIS-AST-31546/2017 and Project No. UIDB/00099/2020. M.S. is supported by grants from the VILLUM FONDEN (grant number 28021) and the Independent Research Fund Denmark (IRFD; 8021-00170B). F.F. acknowledges support from the National Agency for Research and Development (ANID) grants: BASAL Center of Mathematical Modelling AFB-170001, Ministry of Economy, Development, and Tourism’s Millennium Science Initiative through grant IC12009, awarded to the Millennium Institute of Astrophysics, and FONDECYT Regular #1200710. L.G. acknowledges financial support from the Spanish Ministry of Science, Innovation and Universities (MICIU) under the 2019 Ramón y Cajal program RYC2019-027683 and from the Spanish MICIU project PID2020-115253GA-I00. P.H. acknowledges the support by National Science Foundation (NSF) grant AST-1715133.

Background/aim HER2-positive breast cancers eventually relapse in about one third of patients. Is anti-HER2-directed therapy with Herceptin® (trastuzumab) effective in re-treatment? Between 2008 and 2018, 216 patients with recurrent HER2-positive breast cancer (BC) were re-treated with Herceptin (HER) during first-line therapy. This study assessed the effectiveness and tolerability of re-treatment with HER. Patients and methods After approval from Ethical committee, the NIS was conducted according to German Drug Act. Re-treatment with HER was documented at routine visits starting with a basic observational period of maximum 12 months and a follow-up period of maximum additional four years. Results HER2-positive BC relapsed after a median of 36.5 months (mos). Patients were re-treated with HER +/- chemotherapy +/- endocrine therapy. HER-containing regimens resulted in median progression-free survival (mPFS) of 12.7 (95%CI=10.5-14.8) mos and overall survival (OS-2) of 31.6 mos (95%CI=28.8-38.4) since recurrence diagnosis. Differentiation of recurrence types (local, visceral, non-visceral) unfolded worst prognosis for patients with visceral metastases. Cardiac monitoring within this non-interventional study (NIS) did not result in new safety concerns. Conclusion Re-therapy with HER in the first-line setting of advanced HER2-positive breast cancer is effective and without unexpected or intensified adverse events.

The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14–16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast.

This chapter discusses the major steps and issues related to the inclusion of public services in inequality research. Empirically, it investigates how the income distribution in countries changes when the value of publicly provided services to households is included. The authors consider five major categories of public services: education, health care, social housing, childcare and elderly care. On average across OECD countries, spending on these ‘in-kind’ benefits accounts for about 13% of GDP, slightly more than the spending on cash transfers – but with considerable cross-country variation. Broadening the income concept to account for in-kind benefits considerably increases households’ economic resources. But public services also contribute to reducing income inequality, by between one-fifth and one-third depending on the inequality measure. This chapter suggests that publicly provided services fulfil an important direct redistributive role in OECD countries.

In Smith et al. we published estimates of the volumetric rate of supernovae within 100 Mpc. These were incorrect and we present the correct values in this corrigendum.

Background BRAWO is a German non-interventional study of 3000 patients (pts) with advanced/metastatic, hormone-receptor-positive and HER2-negative breast cancer treated with everolimus and exemestane (EVE+EXE). The pivotal BOLERO-2 trial demonstrated that adding EVE to EXE improved PFS over EXE and was generally well tolerated in elderly patients with HR+ advanced breast cancer (>65 years as well as >70 years). Here we describe data of elderly patients treated with EVE+EXE in daily clinical routine. Methods We report data of the 3rd preplanned interim analysis (IA) of the first 1300 pts documented in BRAWO. Patient and disease characteristics in elderly patients (≥ 70 years, n=485) and patients Results At time of data cut-off, 71% pts had discontinued the study, 29% were still ongoing. Patient and disease characteristics were comparable in both groups except for: median age (60y (range: 20-69y) vs. 75y (range 70-93y)), median time since 1st diagnosis (6.4y More patients in the older group received fulvestrant (20.6% vs. 16.2%), in the younger group more patients received chemotherapy (20.3% vs. 14.2%) as last antineoplastic therapy. In general, more patients in the older subgroup did not receive any chemotherapy as pretreatment (53.6% vs 40.2%). More patients in the subgroup ≥70y received 5mg EVE as starting dose (30.3% vs. 20.8%) and had 5mg as end dose (37.9% vs. 26.9%). Median PFS was 7.1 months in the overall population, 7.0 months (6.5, 8.0; 95%CI) for pts Table 1: Incidence and severity of stomatitis Patient Characteristics< 70 years (n=813)≥ 70 years (n=485)Stomatitis Number of patients with at least one Stomatitis Event (based on stomatitis questionnaires)339 (41.7%)200 (41.2%)Grade 1181 (22.3%)95 (19.6%)Grade 2119 (14.6%)79 (16.3%)Grade 319 (2.3%)11 (2.3%)unknown20 (2.5%)15 (3.1%)Number of Stomatitis Events431 (100.0%)252 (100%)Grade 1237 (55.0%)125 (49.6%)Grade 2136 (31.6%)87 (34.5%)Grade 319 (4.4%)13 (5.2%) Discussion The data described here show that EVE+EXE treatment is effective and safe for elderly patients in daily clinical routine. This is consistent with data from an exploratory analysis of the pivotal BOLERO-2 trial, where the same differences in baseline characteristics were observed for elderly pts compared to younger pts as in BRAWO. Efficacy was also comparable to elderly pts in BOLERO-2 (mPFS 6.8 months for EVE+EXE in pts ≥70 years). Citation Format: Tesch H, Grischke E-M, Fasching PA, Decker T, Uleer C, Schneeweiss A, Salat C, Wimberger P, Mundhenke C, Förster F, Kluth-Pepper B, Schubert J, Bloch W, Jackisch C, Schütz F, Lüftner D. Results of the 3rd interim analysis of the non-interventional trial BRAWO – Subanalysis of patients

Background HER2 overexpression occurs in approx. 20% of breast tumors and is associated with increased aggressiveness and mortality. Anti-HER2 re-therapy with trastuzumab (Herceptin®, T) is an established therapeutic option for the treatment of recurrent/metastatic HER2-positive breast cancer (MBC). Patients (pts) receiving T re-therapy appear to benefit from the retreatment after a relapse-free (neo)adjuvant anti-HER2 therapy. Methods This NIS is conducted in Germany to gain additional knowledge about efficacy of 1st-line T retreatment in the clinical routine. 122 sites enrolled a total of 239 pts with locally recurrent and/or MBC who relapsed after (neo)adjuvant treatment with T in their medical history. 230 pts met the eligibility criteria. The current analysis presents data collected between 10/2008-04/2015. Tumor progression was clinically assessed by the investigator. Results Median observation period for the total population (n=230) was 41.7 months (m) (range 0.4-94.5). At start of T retreatment, 20.0% (n=46) of the pts presented with local recurrence only, 79.6% (n=183) presented with distant metastases ± local recurrence and one patient (0.4%) presented with elevated tumor markers. 27.4% (n=63) of the pts developed exclusively non-visceral metastases and 52.2% (n=120) were diagnosed with visceral (± non-visceral) metastases. Median duration of T re-therapy in the first line setting was 9.0 m (95% confidence interval (CI): 7.6-10.1). In 69.6% (n=160) of the cases, T was added to chemotherapy (CT). 15.2% of the pts (n=35) were treated with T+CT + endocrine therapy (ET). A median progression free survival (PFS) of 10.1 m was observed among all eligible patients (n = 230) (95% CI: 8.5-12.0). The evaluation by risk groups revealed a PFS of 23.7 m (95% CI: 13.3-NE*) for patients with local recurrence only, 11.8 m (95% CI: 8.3-20.1) for patients with non-visceral metastases and 7.6 m (95% CI: 6.2-9.9) for patients with visceral metastases. *Not evaluable Median PFS according to treatment regimen was 8.3 m for pts who were treated with T+CT (n=125, 54.3%), 17.7 m in pts who received T+CT+ET (n=35, 15.2%) and 11.2 m in pts treated with T+ET (n=38, 16.5%). Pts who received T monotherapy (n=32, 13.9%) had a median PFS of 13.4 m. Of 230 pts, 121 deaths were documented (52.6%) within the observation period. The median overall survival (OS) was 29.6 m for all pts (95% CI: 27.3-36.8). Median OS was statistically reliable for pts with visceral metastases only: 19.4 m (95% CI: 16.9-27.3). The 2-year survival rate was 62.2% for all pts, 81.9% for pts with local recurrence only, 80.7% for pts with non-visceral metastases and 45.6% for pts with visceral metastases. Conclusions The survival observed for pts with HER2-positive MBC receiving T re-therapy in the clinical routine is in line with the results of recently published data. In terms of the 2-year survival rate, 81.9% of the pts with local recurrence were still alive and thus show the most favourable prognosis. T re-therapy provides an efficient treatment option regardless of given as combination-therapy together with CT and/or ET or as monotherapy. Citation Format: Hanker L, Hitschold T, Grafe A, Förster F, Schröder J, Janssen J, Reichert D, Hielscher C, Keitel S, Hesse T. Efficacy of trastuzumab re-therapy in the clinical routine of HER2-positive breast cancer patients who relapsed after completed anti-HER2 (neo)adjuvant therapy – 5th interim analysis of the national non-interventional study (NIS) ML21589. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-08.

Background BRAWO is a German non-interventional study of 3000 patients (pts) with advanced/metastatic, hormone receptor positive and HER2 negative breast cancer treated with everolimus and exemestane (EVE+EXE). One of the objectives was the documentation of how stomatitis was managed and prevented in clinical routine. We report data of the 3rd preplanned interim analysis (IA) focusing on prophylaxis and management of stomatitis in daily clinical routine. Methods Here we report data of the first 1300 documented pts on efficacy and safety with focus on the adverse event stomatitis. Patient and treatment characteristics were associated with the occurrence of stomatitis. Furthermore chosen treatments for the management of stomatitis are described. Results At time of data cut-off 71% pts had discontinued the study, 29% were still under therapy. Patient and tumor characteristics were reported previously. The most commonly reported AEs of any grade were stomatitis (41.5%), fatigue (14.6%), nausea (12.2%), diarrhea (12.1%), dyspnea (11.3%). 75.2% of stomatitis events occurred during the first 5 weeks of treatment, regardless of the chosen starting dose 5 mg or 10 mg EVE per day. Median duration of a stomatitis episode was 28 days for 5 mg EVE start dose and 23 days for 10mg. However, there was a numerically lower stomatitis incidence and less severe intensity of stomatitis for a start dose of 5 mg vs 10 mg (Table 1). Table 1: Stomatitis incidence and severity by EVE start dose: Worst intensitiy of stomatitisTotal (n=1300)Start dose 5mg (n=316)Start dose 10mg (n=975)Other* (n=9)Number (%) of pts with at least one stomatitis event (any grade)513 (41.5)115 (36.4)421 (43.2)3 (33.3)Grade 1276 (21.2)73 (23.1)202 (20.7)1 (11.1)Grade 2198 (15.2)31 (9.8)165 (16.9)2 (22.2)Grade 330 (2.3)3 (0.9)27 (2.8)0Unknown35 (2.7)8 (2.5)27 (2.8)0*Other includes 2.5mg (n=3), 7.5mg (n=2), 15mg (n=1), 20mg(n=2), 30mg (n=1) 86.5% of pts received recommendations regarding stomatitis prophylaxis. The most frequent recommendations were: mild dental hygiene (e.g. soft toothbrush) (74.8%), avoidance of hot, sour or salty food (70.9%), rinsing with tea (61.7%), and cooling (e.g. sucking ice or frozen pineapple) (56,6%). At least one therapeutic measure was documented for 85.5% of stomatitis events. The most common therapeutic measures were non-drug mouthwash solution (58.3%), cooling (34.7%) or drug intervention (31.9%). Temporary EVE dose adjustments due to stomatitis were done in 11.6% of stomatitis events, temporary dose interruptions in 21.8%, respectively. Efficacy of EVE+EXE seemed to be independent of stomatitis occurrence within 8 weeks after therapy start: mPFS 6.9 months (95%CI, 6.4-8.0) without stomatitis, mPFS 7.4 months (95%CI, 6.3-8.6) with stomatitis. Discussion The percentage of patients with any grade stomatitis was lower in BRAWO (41.5%) than in the pivotal BOLERO-2 trial (59%), which might be explained by increased awareness and experience of treating physicians for prophylaxis and management of this type of adverse event under treatment with EVE+EXE. Most stomatitis events occurred during the first 5 weeks of treatment, which is consistent with data from BOLERO-2. Citation Format: Schütz F, Grischke E-M, Decker T, Uleer C, Schneeweiss A, Salat C, Wimberger P, Mundhenke C, Förster F, Kluth-Pepper B, Schubert J, Bloch W, Tesch H, Jackisch C, Lüftner D, Fasching PA. Stomatitis in patients treated with everolimus and exemestane - Results of the 3rd interim analysis of the non-interventional trial BRAWO. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-08.

Introduction BRAWO is a non-interventional study collecting data of 3000 breast cancer patients treated with everolimus and exemestane (advanced or metastatic, hormone-receptor-positive, HER2-negative breast cancer). We introduce results of the 3rd preplanned interim analysis with data cut-off 08/01/ 2015, including 1300 patients. Since physical activity/exercise was reported to influence side effects as well as quality of life (QoL) of various cancer types and therapies, this analysis focuses on the impact of the physical activity/exercise history, development on adverse effects (AE) of the medical treatment and QoL. Methods Patients were asked to complete the EORTC QLQ-C30 QoL questionnaire and visual analogue scales (VAS-KAS) measuring their present-, past ten year- and lifetime physical activity/exercise level. To differentiate between activity/exercise levels, VAS were divided in three equal components (inactive, somewhat active, very active). Questionnaires and information about AE (e. g. stomatitis, fatigue, nausea, diarrhea, etc.) were collected before starting the medical treatment and were repeated each three months. Logistic regression model was used to estimate the impact of baseline physical activity/exercise on AE at any time point of the therapy. ANOVA models were used to calculate the impact of the baseline activity/exercise level on QoL at the last completed data set of each patient. Results Median age of patients was 66 years, median weight was 70 kg, median BMI was 25.9, median time since primary diagnosis was 6.2 years, and 54.4% had visceral metastases at baseline. The median PFS for the first 1300 patients was 7.1 months (95% CI, 6.5-8.0). Patients who reported to be very active (exercise) at the week prior to baseline (4.4%) showed significant lower numbers of AE compared to patients who indicate to be somewhat (14.8%) or inactive (80.8%). In contrast to the exercise level, physical activity in everyday life did not affect the AE incidence. Neither lifetime nor past ten year activity/exercise level is associated with the occurrence of AE. Regarding QoL, very active as well as somewhat active women (measured at baseline for almost each time period) showed significant higher QoL values compared to inactive women during the last assessment before death/progress. Conclusion Exercise prior to medical treatment with Everolimus and Exemestane may impact AE during therapy. Since physical activity did not show such a relation, this analysis highlights the importance of specific guidelines for preventive/rehabilitative exercise programs. More knowledge about dose-response relationships is needed. Furthermore a livelong healthy, "active" lifestyle may increase QoL, even in patients with advanced and terminal breast cancer disease. Citation Format: Bloch W, Baumann F, Zimmer P, Grischke E-M, Fasching PA, Decker T, Uleer C, Schneeweiss A, Salat C, Wimberger P, Mundhenke C, Förster F, Kluth-Pepper B, Schubert J, Tesch H, Schütz F, Lüftner D, Jackisch C. Impact of physical activity/exercise on adverse events and quality of life during treatment with everolimus and exemestane for ER+ women - Results of the 3rd interim analysis of BRAWO. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-07.

Introduction BRAWO is a German non-interventional study of 3000 patients (pts) with advanced or metastatic, hormone-receptor-positive, HER2-negative breast cancer treated with everolimus (EVE) and exemestane (EXE). We report results of the 2nd preplanned interim analysis (IA) with a data cut-off on 8th July 2014. Methods BRAWO collects data on the routine clinical treatment with EVE and EXE at about 400 sites. Main objectives are to extend the knowledge on a) the efficacy in the clinical routine and the impact of physical activity on efficacy and quality of life, b) prophylaxis and management of stomatitis, and c) the sequence of therapy in the clinical routine. The 2nd IA was defined to take place 12 months after the inclusion of the 500. patient into the documentation. Results Efficacy data will be reported for the first 500 documented pts. Apart from data on the total study population we will present the PFS results for subgroups including pts with or without prior EXE therapy, with or without prior chemotherapy for the advanced setting, with or without visceral metastasis and with regard to the line of treatment in the advanced setting and the extent of physical activity. The respective summary of adverse events for these patients will be presented as well as results on treatment compliance and dosing. Baseline characteristics and medical history as well as insights into treatment sequences before EVE and EXE will further be shown for all enrolled patients with valid baseline documentation (approx. 1200). Conclusion This subgroup analysis will provide insights into the treatment efficacy in the clinical routine and will add to a more comprehensive understanding of the treatment with EVE/EXE. Citation Format: Christian Jackisch, Eva-Maria Grischke, Andreas Schneeweiss, Thomas Decker, Christoph Uleer, Frank Förster, Oliver Tomé, Pauline Wimberger, Christian M Kurbacher, Bettina Mueller, Nadia Harbeck, Christoph Mundhenke, Sherko Kuemmel, Mathias Muth, Julia Kreuzeder, Wilhelm Bloch, Hans Tesch, Diana Lüftner, Florian Schütz, Peter A Fasching. Subgroup analysis on efficacy in the routine treatment - Results of the 2nd interim analysis of BRAWO, the non-interventional trial "Breast Cancer Treatment with Everolimus and Exemestane for HR+ Women" [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-12.

Die Vereinzelung textiler Zuschnitte vom Halbzeugstapel stellt die Automatisierungstechnik seit jeher vor große Herausforderungen. Am Markt verfügbare Greifer sind oft nicht in der Lage, den Erfolg dieser Handhabungsoperation zu bestätigen und beeinflussen die Prozesssicherheit negativ. In Kooperation zwischen der J. Schmalz GmbH und dem wbk Institut für Produktionstechnik wurde ein Ansatz entwickelt, um den Erfolg beim Vereinzeln textiler Kohlenstofffaserhalbzeuge zu beurteilen. The separation of fabrics from a stack has always been a major challenge in the automation technology. Grippers available on the market are unable to confirm the success of this operation and influence the process negatively. In cooperation between the J. Schmalz GmbH and the Institute of Production Science wbk an approach was developed to evaluate the success of fabric separation processes.

Time- and space-resolved measurements of temperature and pressure in flames and engines using laser induced grating scattering from fuels, tracer species and combustion products are reported with precisions in the range 0.1-3%.

This article assesses various underlying driving factors for the evolution of household earnings inequality for 23 OECD countries from the mid-1980s to the mid-2000s. There are a number of factors at play. Some are related to labour market trends – increasing dispersion of individual wages and changes in men’s and women’s employment rates. Others relate to shifts in household structures and family formation – more single-headed households and increased earnings correlation among partners in couples. The contribution of each of these factors is estimated using a semi parametric decomposition technique. The results reveal that marital sorting and household structure changes contributed, albeit moderately, to increasing household earnings inequality, while rising women’s employment exerted a sizable equalising effect. However, changes in labour market factors, in particular increases in men’s earnings disparities, were identified as the main driver of household earnings inequality, contributing between one-third and one-half to the overall increase in most countries. Sensitivity analysis applying a reversedorder decomposition suggests that these results are robust.

Background: Bevacizumab (BEV) combined with chemotherapy (CT) significantly improves progression-free survival (PFS) and response rate (RR) vs CT alone in the 1st-line treatment of HER2-negative metastatic breast cancer (mBC). BEV was continued for ≥1 year in 20% of patients (pts) in the global ATHENA safety study. We examined a similar subgroup of pts with long-term antibody treatment in a large German observation study. Meanwhile, long-term follow-up of up to 4.5 years allows to present the final results, including mature data on overall survival. Methods: Pts who had received no prior CT for their mBC received BEV-PAC per the European label. Efficacy and safety were documented in detail for up to 1 year (or until progression, death, or BEV discontinuation if earlier), with subsequent retrieval of long-term follow-up. Results: By April 2013, final data were available for 865 pts, of whom 167 (20%) were recorded to have received BEV for ≥1 year. Baseline characteristics of this subset relative to the overall population are summarized in the table. CharacteristicOverall population (n = 865)Subgroup treated with BEV for ≥1 year (n = 167)Median age, years (range)58(26-87)57(28-79)Age ≥65 years,%3230Metastatic at diagnosis,%2018Disease-free inreval 1,%98Prior (neo)adjuvant chemotherapy,%6661*n = 591, initially M0. #n = 113 Dose reductions of long-term BEV occurred in only 3% of cycles and (at least once) in 17% of pts. In the majority of pts treated for ≥1 year, BEV was continued as a single agent after discontinuation of CT. The overall best RR in pts treated for ≥1 year was 80% (complete response in 19%). Median PFS, based on observed events in 83% of all pts, was 18.4 months compared to 9.6 months in the overall population. Overall survival data, based on 524 deaths (61%), show a median of 21.6 months. In the subgroup with prolonged therapy, median OS amounts to 35.7 months with 40% of pts still alive after 4 years. Safety of long-term BEV is as previously reported with only a slightly increased hypertension rate (35%, grade ≥3: 11%), and no cases of gastrointestinal perforation, arterial thromboembolic event, or reversible posterior leukoencephalopathy syndrome. Conclusions: According to the mature data of this study, including those on OS, a notable proportion of pts appear to derive benefit from prolonged exposure to first-line BEV-containing therapy. Although baseline characteristics exhibited only moderate indicators for an a priori more favorable prognostic profile in the subset of pts treated for ≥1 year, of course one has to keep in mind, that time-related efficacy data are biased towards improved outcome in those able to continue BEV for ≥1 year. However, the median survival of almost 3 years suggests that in a considerable number of pts continued first-line BEV-PAC correlates to favorable outcomes with limited adverse effects. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-03.

Sub-monolayers of Eu oxide were grown on Ni(100) and analysed by means of in-situ scanning tunnelling microscopy and low energy electron diffraction. For changes of the O 2 pressure not more than a factor of two, four different surface phases were found which consist of EuO(111), ‘magic’ clusters and two 2-dimensional nano-layers without a counterpart in bulk Eu oxides. A structural model for one of the latter phases suggests an O–O nearest neighbour (NN) distance of 4.4 A — considerably larger than the 3.64 A for bulk EuO.

The effect of grazing incidence 4 keV Ar+ ion irradiation on the early stage of Ag thin film growth on amorphous Si was investigated. The double effect of axial and surface channeling resulted in grains oriented along the 〈110〉 axis in-plane, while the (111) out-of-plane texture was maintained. A slight average tilt of the (111) out-of-plane texture axis towards the ion beam direction is proposed to result from the difference between terrace and step edge sputtering yield. The observed tilt is consistent with a minimum erosion orientation of the surface profile.

Several natural compound interfere with microtubules or the actin cytoskeleton. Compounds interfering with the microtubules like Vinca-alkaloids or taxanes, are extensively used for cancer therapy. In contrast, knowledge about pharmacological properties of actin binding drugs is poor and drugs interfering with actin are far from clinical use. Rhizopodin is a natural compound that strongly affects the actin cytoskeleton at nanomolar concentrations. Initial work revealed interesting anti-bacterial and cytotoxic effects, but the cellular effects and pharmacological properties of rhizopodin have not been characterized. We hypothesized that rhizopodin might exert anti-cancer activity. Therefore, the aim of this study was to characterize the cellular and pharmacological effects of rhizopodin in cancer. Effects of rhizopodin demonstrated prominent effects on the actin cytoskeleton as shown in the actin-pyrene assay and by immunostaining of cancer cells. To investigate cellular effects of rhizopodin, we analyzed cell proliferation, cell death induction by propidium iodide exclusion and western blot, as well as migration by impedance measurement using the xCELLligence device in MDA-MB-231 breast cancer and T24 bladder cancer cell lines. Rhizopodin inhibited proliferation and induced cell death of MDA-MB-231 and T24 cells at nanomolar concentrations. PARP cleavage by rhizopodin suggests caspase-dependent cell death induction. Importantly, rhizopodin potently inhibited MDA-MB-231 and T24 cancer cell migration at subtoxic doses where no actin aggregation was observed, indicating a specific underlying signaling of rhizopodin. In summary, our study elucidates rhizopodin as actin-binding natural compound that exerts potent anti-cancer effects. Therefore, our work provides the basis for further in depth characterization of rhizopodin as an antitumoral agent.

This chapter provides a thorough survey of what recent international (i.e., cross-country) studies can tell us about the multiple causes of income inequality in the OECD area with regard to both levels and trends. The survey covers economics literature in particular but also relevant evidence from sociology and political science. We provide an overview of drivers of inequality in six areas: (i) structural macroeconomic sectoral changes, (ii) globalization and technology change, (iii) labor market and other relevant institutions, (iv) politics and political processes, (v) tax/transfer schemes, and (vi) demographic and other microstructural changes. We find that the literature, while extremely rich in partial analysis of all six areas, provides very few analyses with truly multivariate and multicountry specifications for the joint section of the OECD and EU countries. Suggestions include more cross-discipline reflections on various findings. This is now well facilitated by the spectacular development of data, as well as in relation to methodological harmonization across disciplines.

The article focuses on apprehending and comparing poverty in the context of the recent enlargement of the European Union. In particular, it discusses how alternative measures of poverty in an enlarged Europe could take into account both income and non-income aspects and the extent to which comparative measures of consistent poverty reflect country-specific versus European-wide thresholds. These measures are analysed and applied to survey data from the former EU-15 and three new EU member states – the Czech Republic, Hungary and Slovenia. The socio-demographic poverty profiles identified in Central Eastern European countries are similar to those of other EU member states, with the exception of a relatively lower relative poverty risk for youth in the new EU countries. On the other hand, unemployment constitutes the strongest risk factor for falling into poverty, be it defined as monetary, non-monetary or consistent poverty, equally in older and new EU countries. The empirical findings indicate important me...