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

Solarthermische Kraftwerke

[PDF] von wupperinst.org Solarthermische Kraftwerke Autoren Robert Pitz-Paal, Thomas Wetzel, Peter Nitz, Julia C Terrapon-Pfaff, Thomas Fink, Ole Soukup Publikationsdatum 2018/7/10 Beschreibung Der Schutz des Klimas und die dafür erforderliche Umstellung der Energieversorgung auf erneuerbare Energien ist eine globale Herausforderung, welche nach maßgeschneiderten Lösungen für die unterschiedlichen Klimazonen und Märkte der Erde verlangt. Die verstärkte Solarenergienutzung spielt dabei eine maßgebliche Rolle. Die Rolle Deutschlands als Exportnation beschränkt sich hierbei nicht auf die Klimawende im eigenen Land, sondern beinhaltet auch den weltweiten Export erneuerbarer Energietechnologien. Die Kosten der photovoltaischen Stromerzeugung (PV) und der Windkraft sind in den vergangenen Jahren erfreulicherweise deutlich gesunken, entsprechend wurden in vielen Ländern große Kapazitäten zugebaut. Die resultierende stark gestiegene Einspeisung fluktuierender Erzeuger stellt Netzbetreiber vor neue Herausforderungen, insbesondere durch die extremen Lastschwankungen für plan-und steuerbare, heute größtenteils fossil befeuerte konventionelle Kraftwerke

The PyCBC search for gravitational waves from compact binary coalescence

We describe the PyCBC search for gravitational waves from compact-object binary coalescences in advanced gravitational-wave detector data. The search was used in the first Advanced LIGO observing run and unambiguously identified two black hole binary mergers, GW150914 and GW151226. At its core, the PyCBC search performs a matched-filter search for binary merger signals using a bank of gravitational-wave template waveforms. We provide a complete description of the search pipeline including the steps used to mitigate the effects of noise transients in the data, identify candidate events and measure their statistical significance. The analysis is able to measure false-alarm rates as low as one per million years, required for confident detection of signals. Using data from initial LIGO's sixth science run, we show that the new analysis reduces the background noise in the search, giving a 30% increase in sensitive volume for binary neutron star systems over previous searches.Comment: 29 pages, 7 figures, accepted by Classical and Quantum Gravit

Solarthermische Kraftwerke

Der Schutz des Klimas und die dafür erforderliche Umstellung der Energieversorgung auf erneuerbare Energien ist eine globale Herausforderung, welche nach maßgeschneiderten Lösungen für die unterschiedlichen Klimazonen und Märkte der Erde verlangt. Die verstärkte Solarenergienutzung spielt dabei eine maßgebliche Rolle. Die Rolle Deutschlands als Exportnation beschränkt sich hierbei nicht auf die Klimawende im eigenen Land, sondern beinhaltet auch den weltweiten Export erneuerbarer Energietechnologien. Die Kosten der photovoltaischen Stromerzeugung (PV) und der Windkraft sind in den vergangenen Jahren erfreulicherweise deutlich gesunken, entsprechend wurden in vielen Ländern große Kapazitäten zugebaut. Die resultierende stark gestiegene Einspeisung fluktuierender Erzeuger stellt Netzbetreiber vor neue Herausforderungen, insbesondere durch die extremen Lastschwankungen für plan- und steuerbare, heute größtenteils fossil befeuerte konventionelle Kraftwerke. Hier bieten solarthermische Kraftwerke Lösungen

“A very orderly retreat”: Democratic transition in East Germany, 1989-90

East Germany's 1989-90 democratisation is among the best known of East European transitions, but does not lend itself to comparative analysis, due to the singular way in which political reform and democratic consolidation were subsumed by Germany's unification process. Yet aspects of East Germany's democratisation have proved amenable to comparative approaches. This article reviews the comparative literature that refers to East Germany, and finds a schism between those who designate East Germany's transition “regime collapse” and others who contend that it exemplifies “transition through extrication”. It inquires into the merits of each position and finds in favour of the latter. Drawing on primary and secondary literature, as well as archival and interview sources, it portrays a communist elite that was, to a large extent, prepared to adapt to changing circumstances and capable of learning from “reference states” such as Poland. Although East Germany was the Soviet state in which the positions of existing elites were most threatened by democratic transition, here too a surprising number succeeded in maintaining their position while filing across the bridge to market society. A concluding section outlines the alchemy through which their bureaucratic power was transmuted into property and influence in the “new Germany”

Evidence-based guidelines for managing patients with primary ER+ HER2− breast cancer deferred from surgery due to the COVID-19 pandemic

Many patients with ER+ HER2- primary breast cancer are being deferred from surgery to neoadjuvant endocrine therapy (NeoET) during the COVID-19 pandemic. We have collated data from multiple international trials of presurgical endocrine therapy in order to provide guidance on the identification of patients who may have insufficiently endocrine-sensitive tumors and should be prioritised for early surgery or neoadjuvant chemotherapy rather than NeoET during or in the aftermath of the COVID-19 pandemic for safety or when surgical activity needs to be prioritized. For postmenopausal patients, our data provide strong support for the use of ER and PgR status at diagnosis for triaging of patients into three groups in which (taking into account clinical factors): (i) NeoET is likely to be inappropriate (Allred ER 10%) indicates a higher priority for early surgery. Too few data were available for premenopausal patients to provide a similar treatment algorithm. These guidelines should be helpful for managing patients with early ER+ HER2- breast cancer during and in the aftermath of the COVID-19 crisis

70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.

The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.)

Auf dem Weg zur klimaneutralen Industrie - Herausforderungen und Strategien

Der Beitrag beleuchtet die Herausforderungen und Strategien für die Industrie in Deutschland im Rahmen der Energiewende. Der Fokus liegt hierbei auf den Themen Kreislaufwirtschaft, Wasserstoffnutzung, Erneuerbare Prozesswärme und Bioenergie sowie auf den sich darausergebenden Herausforderungen an die Infrastruktur und die Politik