Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial

BACKGROUND The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting. Micrometastases are dependent on angiogenesis, suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting. We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer. METHODS For this open-label, randomised phase 3 trial we recruited patients with centrally confirmed triple-negative operable primary invasive breast cancer from 360 sites in 37 countries. We randomly allocated patients aged 18 years or older (1:1 with block randomisation; stratified by nodal status, chemotherapy [with an anthracycline, taxane, or both], hormone receptor status [negative vs low], and type of surgery) to receive a minimum of four cycles of chemotherapy either alone or with bevacizumab (equivalent of 5 mg/kg every week for 1 year). The primary endpoint was invasive disease-free survival (IDFS). Efficacy analyses were based on the intention-to-treat population, safety analyses were done on all patients who received at least one dose of study drug, and plasma biomarker analyses were done on all treated patients consenting to biomarker analyses and providing a measurable baseline plasma sample. This trial is registered with ClinicalTrials.gov, number NCT00528567. FINDINGS Between Dec 3, 2007, and March 8, 2010, we randomly assigned 1290 patients to receive chemotherapy alone and 1301 to receive bevacizumab plus chemotherapy. Most patients received anthracycline-containing therapy; 1638 (63%) of the 2591 patients had node-negative disease. At the time of analysis of IDFS, median follow-up was 31·5 months (IQR 25·6-36·8) in the chemotherapy-alone group and 32·0 months (27·5-36·9) in the bevacizumab group. At the time of the primary analysis, IDFS events had been reported in 205 patients (16%) in the chemotherapy-alone group and in 188 patients (14%) in the bevacizumab group (hazard ratio [HR] in stratified log-rank analysis 0·87, 95% CI 0·72-1·07; p=0·18). 3-year IDFS was 82·7% (95% CI 80·5-85·0) with chemotherapy alone and 83·7% (81·4-86·0) with bevacizumab and chemotherapy. After 200 deaths, no difference in overall survival was noted between the groups (HR 0·84, 95% CI 0·64-1·12; p=0·23). Exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevacizumab (Cox interaction test p=0·029). Use of bevacizumab versus chemotherapy alone was associated with increased incidences of grade 3 or worse hypertension (154 patients [12%] vs eight patients [1%]), severe cardiac events occurring at any point during the 18-month safety reporting period (19 [1%] vs two [<0·5%]), and treatment discontinuation (bevacizumab, chemotherapy, or both; 256 [20%] vs 30 [2%]); we recorded no increase in fatal adverse events with bevacizumab (four [<0·5%] vs three [<0·5%]). INTERPRETATION Bevacizumab cannot be recommended as adjuvant treatment in unselected patients with triple-negative breast cancer. Further follow-up is needed to assess the potential effect of bevacizumab on overall survival.

A New Velocity Map for Byrd Glacier, East Antarctica, from Sequential Aster Satellite Imagery

New ice-velocity measurements are obtained for the main trunk of Byrd Glacier, East Antarctica, using recently acquired Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) imagery. The velocities are derived from the application of a cross-correlation technique to sequential images acquired in 2000 and 2001. Images were co-registered and ortho-rectified with the aid of a digital elevation model (DEM) generated from ASTER stereo imagery. This paper outlines the process of DEM generation, image co-registration and correction, and the application of the cross-correlation technique to obtain ice velocities. Comparison of the new velocity map with earlier measurements of velocity from 1978 indicates that the glacier has undergone a substantial deceleration between observations. Portions of the glacier flowing at speeds of similar to 850 m a(-1) in 1978/79 were flowing at similar to 650 m a(-1) in 2000/01. The cause of this change in ice dynamics is not known, but the observation shows that East Antarctic outlet glaciers can undergo substantial changes on relatively short timescales.

A 700 Year Record of Southern Hemisphere Extratropical Climate Variability

Annually dated ice cores from West and East Antarctica provide proxies for past changes in atmospheric circulation over Antarctica and portions of the Southern Ocean, temperature in coastal West and East Antarctica, and the frequency of South Polar penetration of El Nino events. During the period (AD) 1700-1850, atmospheric circulation over the Antarctic and at least portions of the Southern Hemisphere underwent a mode switch departing from the out-of-phase alternation of multi-decadal long phases of EOF1 and EOF2 modes of the 850 hPa field over the Southern Hemisphere (as defined in the recent record by Thompson and Wallace, 2000; Thompson and Solomon, 2002) that characterizes the remainder of the 700 year long record. From (AD) 1700 to 1850, lower-tropospheric circulation was replaced by in-phase behavior of the Amundsen Sea Low component of EOF2 and the East Antarctic High component of EOF1. During the first phase of the mode switch, both West and East Antarctic temperatures declined, potentially in response to the increased extent of sea ice surrounding both regions. At the end of the mode switch, West Antarctic coastal temperatures rose and East Antarctic coastal temperatures fell, respectively, to their second highest and lowest of the record. Polar penetration of El Nino events increased during the mode switch. The onset of the AD 1700-1850 mode switch coincides with the extreme state of the Maunder Minimum in solar variability. Late 20th-century West Antarctic coastal temperatures are the highest in the record period, and East Antarctic coastal temperatures close to the lowest. Since AD 1700, extratropical regions of the Southern Hemisphere have experienced significant climate variability coincident with changes in both solar variability and greenhouse gases.

"Quasi ombra e figura de la verità". Poesia e pensiero in Torquato Tasso

"Pochi autori come il Tasso hanno suscitato interpretazioni tanto differenziate e, in molti casi, discordanti. Posto di volta in volta a chiusura di un'epoca, quella manieristica, o come anticipatore della successiva temperie barocca, egli pare aver scontato il prezzo di un'esemplarità sin troppo manifesta rispetto al proprio Zeitgeist, una stagione che vede, nella vulgata storiografica, la regola prevalere sull'afflato creativo. 'Era già critico prima di esser poeta', sentenziò il De Sanctis, che arrivava a circoscriverne pure l'esperienza biografica nel perimetro di un implacabile autodafé, definendolo 'più crudele inquisitore di sé che il tribunale dell'Inquisizione'. A ciò poi si aggiungeva l'estrinsecità della corte quale destinataria e quasi principio informativo del mondo tassiano, che sembrava legittimare, da Croce in avanti, tutta una serie di giudizi limitativi sulla sua poesia, orientati ad accentuarne la natura encomiastica, aneddotica, addirittura frivola. La critica più recente ha compiuto un'imponente e fondamentale opera di scavo all'interno della cultura tassiana, delle sue letture, della sua poetica, ma il tentativo di rettificare il profilo complessivo dell'autore mostra esiti ancora incerti. In risposta alla vecchia immagine di un Tasso sconfitto dalla cultura controriformistica e alla fine assoggettato alle sue leggi, se ne sono di recente aggiunte altre..." (Dall'introduzione)

Tintenfass und Teleskop. Galileo Galilei im Schnittpunkt wissenschaftlicher, literarischer und visueller Kulturen im 17. Jahrhundert

Die Figur Galileo Galilei ist für die europäische Wissenschaftsgeschichte, für die Kulturwissenschaften und für eine wissensgeschichtlich orientierte Literatur- und Kunstwissenschaft von großem Interesse. In diesem Band werden die Überschneidungen, Wechselwirkungen und Transferprozesse zwischen den wissenschaftlichen und kulturellen Dimensionen untersucht, die für Galileis Profilierung als frühneuzeitlicher Wissenschaftler ebenso wichtig sind wie für die im weiteren Sinn kulturelle Wahrnehmung seiner Entdeckungen und seiner Schriften – vor allem in Literatur und Kunst. Der Band ist interdisziplinär konzipiert, um die fachlichen Einzelperspektiven von Literatur-, Kunst- und Kulturwissenschaftlern sowie Wissenschaftshistorikern zusammenzuführen. Analysiert werden Formen und Funktionen der Produktion, Konzeptualisierung und Repräsentation von Wissen sowie Aspekte der Diskussion und Diffusion von Galileis Wissensansprüchen im Kontext der Frühen Neuzeit. Mit dieser Fokussierung auf die im Schnittbereich verschiedener kultureller Formationen angesiedelte Etablierung Galileis liefert der Band somit einen Beitrag zur interdisziplinären Erforschung von Galileis Rolle und Rezeption in der europäischen Kultur- und Wissensgeschichte des 17. Jahrhunderts. Sprachen: Deutsch, Englisch, Italienisch

Eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia have similar clinical, endoscopic and histological findings.

BACKGROUND Some patients with a phenotypic appearance of eosinophilic oesophagitis (EoE) respond histologically to PPI, and are described as having PPI-responsive oesophageal eosinophilia (PPI-REE). It is unclear if PPI-REE is a GERD-related phenomenon, a subtype of EoE, or a completely unique entity. AIM To compare demographic, clinical and histological features of EoE and PPI-REE. METHODS Two databases were reviewed from the Walter Reed and Swiss EoE databases. Patients were stratified into two groups, EoE and PPI-REE, based on recent EoE consensus guidelines. Response to PPI was defined as achieving less than 15 eos/hpf and a 50% decrease from baseline following at least a 6-week course of treatment. RESULTS One hundred and three patients were identified (63 EoE and 40 PPI-REE; mean age 40.2 years, 75% male and 89% Caucasian). The two cohorts had similar dysphagia (97% vs. 100%, P = 0.520), food impaction (43% vs. 35%, P = 0.536), and heartburn (33% vs. 32%, P = 1.000) and a similar duration of symptoms (6.0 years vs. 5.8 years, P = 0.850). Endoscopic features were also similar between EoE and PPI-REE; rings (68% vs. 68%, P = 1.000), furrows (70% vs. 70%, P = 1.000), plaques (19% vs. 10%, P = 0.272), strictures (49% vs. 30%, P = 0.066). EoE and PPI-REE were similar in the number of proximal (39 eos/hpf vs. 38 eos/hpf, P = 0.919) and distal eosinophils (50 vs. 43 eos/hpf, P = 0.285). CONCLUSIONS EoE and PPI-responsive oesophageal eosinophilia are similar in clinical, histological and endoscopic features and therefore are indistinguishable without a PPI trial. Further studies are needed to determine why a subset of patients with oesophageal eosinophilia respond to PPI.