Endoscopic management of patients with high-risk colorectal colitis–associated neoplasia:a Delphi study

Background and Aims: Current guidelines recommend endoscopic resection of visible and endoscopically resectable colorectal colitis–associated neoplasia (CAN) in patients with inflammatory bowel disease (IBD). However, patients with high-risk CAN (HR-CAN) are often not amenable to conventional resection techniques, and a consensus approach for the endoscopic management of these lesions is presently lacking. This Delphi study aims to reach consensus among experts on the endoscopic management of these lesions. Methods: A 3-round modified Delphi process was conducted to reach consensus among worldwide IBD and/or endoscopy experts (n = 18) from 3 continents. Consensus was considered if ≥75% agreed or disagreed. Quality of evidence was assessed by the criteria of the Cochrane Collaboration group. Results: Consensus was reached on all statements (n = 14). Experts agreed on a definition for CAN and HR-CAN. Consensus was reached on the examination of the colon with enhanced endoscopic imaging before resection, the endoscopic resectability of an HR-CAN lesion, and endoscopic assessment and standard report of CAN lesions. In addition, experts agreed on type of resections of HR-CAN (20 mm, with or without good lifting), endoscopic success (technical success and outcomes), histologic assessment, and follow-up in HR-CAN. Conclusions: This is the first step in developing international consensus–based recommendations for endoscopic management of CAN and HR-CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of CAN and HR-CAN. The present work and proposed standardization might benefit future studies

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy

Housing supply and brownfield regeneration in a post-Barker review world: A comparison of policy and practice in England and Scotland

The findings of the Barker review, which examined the reasons for the undersupply of UK housing, have important implications for the devolved constituents of the UK, including Scotland. This paper traces the emergence of the brownfield regeneration policy agenda across the UK and examines how the Barker review connects with this brownfield policy focus. The paper compares housing and brownfield policies and practices in England and Scotland, places them in an international context and elicits wider lessons for devolved governance in relation to housing policy, in terms of `centrist—local' tensions. Estimates based on published data suggest that Barker's emphasis on increased housing supply cannot easily be reconciled with the current emphasis on brownfield development and is likely to require a return to greenfield development in both countries

A factor analytic approach to the identification of geomorphic processes from soil particle size characteristics

Q‐mode factor analysis of soil particle size data is used to identify the three dominant geomorphic processes responsible for the spatial variability of particle size in a catchment on the basaltic Darling Downs landsurface. Three factors are shown to account for 95 per cent of the textural variability of a suite of transported and sedentary materials. The spatial characteristics of groups of samples associated with the three factors suggests that the three factors are associated with suspended sediment transport and deposition, weathering, and bedload transport and deposition respectively. These interpretations are supported by the detailed graphical analysis of the cumulative particle size curves. The spatially variable influence of the three factors and related processes is given by their respective factor loadings which are mappable for the surface layer materials. Copyrigh