Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials.

BACKGROUND: REAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that peri-operative epirubicin, cisplatin and infused 5-fluorouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. PATIENTS AND METHODS: Analysis of response rate (RR; the primary end-point of phase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC+P in REAL3 was pre-planned to determine if molecular selection for the on-going study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pre-treatment biopsies and results correlated with response to mEOC+P. Association between these biomarkers and overall survival (OS) was assessed in MAGIC patients to determine any prognostic effect. RESULTS: RR was 52% to mEOC+P, 48% to EOC. Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%), PIK3CA (2.5%) and loss of PTEN expression (15.0%). None of the biomarkers evaluated predicted resistance to mEOC+P. In MAGIC, mutations in KRAS, BRAF and PIK3CA and loss of PTEN (phosphatase and tensin homolog) were found in 6.3%, 1.0%, 5.0% and 10.9%, respectively, and were not associated with survival. CONCLUSIONS: The RR of 52% in REAL3 with mEOC+P met pre-defined criteria to continue accrual to phase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect.

Threshold Magic: Impressionism and the Domestic Interior

This article focuses on the liminal space of the threshold in paintings by female Impressionists. It engages with Cultural theory and History of Design in order to offer a new interpretation of domestic spaces

Complex contests and the influence of aggressiveness in pigs

Animal contests vary greatly in behavioural tactics used and intensity reached, with some encounters resolved without physical contact while others escalate to damaging fighting. However, the reasons for such variation remains to be fully explained. Aggressiveness, in terms of a personality trait, offers a potentially important source of variation that has typically been overlooked. Therefore, we studied how aggressiveness as a personality trait influenced escalation between contestants matched for resource holding potential (RHP), using detailed observations of the contest behaviour, contest dynamics, and escalation levels. We predicted that winner and loser behaviour would differ depending on personality. This was tested by examining 52 dyadic contests between pigs (Sus scrofa). Aggressiveness was assayed in resident-intruder tests prior to the contest. Contests were then staged between pigs matched for RHP in terms of body weight but differing in their aggressiveness. In 27% of the contests a winner emerged without escalated physical fighting, demonstrating that a fight is not a prerequisite between RHP-matched contestants. However, the duration of contests with or without fighting was the same. In contests without a fight, opponents spent more time on mutual investigation and non-contact displays such as parallel walking, which suggests that ritualized display may facilitate assessment and decision making. Winners low in aggressiveness invested more time in opponent investigation and display and showed substantially less aggression towards the loser after its retreat compared to aggressive winners. Aggressiveness influenced contest dynamics but did not predict the level of escalation. Prominent behavioural differences were found for the interaction between personality and outcome and we therefore recommend including this interaction in models where personality is considered. Analyses based on contest duration only would miss many of the subtleties which are shown here and we therefore encourage more detailed analyses of animal contests, irrespective of the level of contest escalation.