Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Financial intermediation and technology: What's old, what's new?

We study the effects of technological change on financial intermediation, distinguishing between innovations in information (data collection and processing) and communication (relationships and distribution). Both follow historic trends towards an increased use of hard information and less inperson interaction, which are accelerating rapidly. We point to more recent innovations, such as the combination of data abundance and artificial intelligence, and the rise of digital platforms. We argue that in particular the rise of new communication channels can lead to the vertical and horizontal disintegration of the traditional bank business model. Specialized providers of financial services can chip away activities that do not rely on access to balance sheets, while platforms can interject themselves between banks and customers. We discuss limitations to these challenges, and the resulting policy implications

Long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases of urachal cancer

Introduction: Urachal adenocarcinoma (UrAC) is a rare malignancy arising from persistent urachal remnants, which can cause peritoneal metastases (PM). Currently, patients with this stage UrAC are considered beyond cure. Our objective is to report long-term oncological outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with PM of urachal adenocarcinoma (UrAC). Materials and methods: We identified 55 patients with UrAC treated at our hospital between 1994 and 2017. Patients were staged with CT, bone scintigraphy and/or PET/CT. From 2001 on, cN0M0 patients underwent staging laparoscopy. Ten patients had PM and were treated with CRS/HIPEC; 35 showed no metastases and underwent local treatment; 10 had distant metastases and received palliative chemotherapy. Disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method and log-rank tests. Postoperative complications represent a secondary outcome. Results: The median follow-up was 96.8 months. Of the CRS/HIPEC patients, 5 (50%) developed a recurrence; 4 (40%) died of disease. The 2-yr and 5-yr DSS after CRS/HIPEC were 66.7% and 55.6%, respectively. DSS of the CRS/HIPEC patients did not significantly differ from DSS of patients without metastases who only underwent curative local treatment and was superior to patients with distant metastases (P = 0.012). The overall complication rate after CRS/HIPEC was 60%. Major complications (Clavien 3) constituted 20%. The study is limited by its retrospective nature and the small sample size. Conclusion: CRS/HIPEC demonstrates satisfactory long-term oncological outcome for patients with PM of UrAC. It may be offered as a potentially curative treatment option for this group of patients

From government to governance: Polish regional development agencies in a changing regional context

This article charts the evolving role of Regional Development Agencies (RDAs) in Poland. It argues that changes to regional institutional and policy environments, linked to processes of regionalisation, EU accession, and the administration of European Union structural funds, have prompted increasing diversification of RDA activities. Moreover, questions of democratic accountability and economic efficiency are becoming increasingly pointed. Has regionalisation boosted the democratic accountability and regional orientation of agencies? Has administrative reform simplified agencies' delivery of development programmes? What influence has the administration of structural funds had on this? The article explores these issues, stressing generally that theoretical analyses of RDA activities must take increasing account of agency "positioning," i.e., their role and purpose in an increasingly crowded and complex regional policy arena. Future scenarios for the evolution of RDAs in Poland are also outlined

Imaging plant growth in 4D : robust tissue reconstruction and lineaging at cell resolution.

International audienceQuantitative information on growing organs is required to better understand morphogenesis in both plants and animals. However, detailed analyses of growth patterns at cellular resolution have remained elusive. We developed an approach, multiangle image acquisition, three-dimensional reconstruction and cell segmentation-automated lineage tracking (MARS-ALT), in which we imaged whole organs from multiple angles, computationally merged and segmented these images to provide accurate cell identification in three dimensions and automatically tracked cell lineages through multiple rounds of cell division during development. Using these methods, we quantitatively analyzed Arabidopsis thaliana flower development at cell resolution, which revealed differential growth patterns of key regions during early stages of floral morphogenesis. Lastly, using rice roots, we demonstrated that this approach is both generic and scalable