Distributed Searchable Symmetric Encryption

Searchable Symmetric Encryption (SSE) allows a client to store encrypted data on a storage provider in such a way, that the client is able to search and retrieve the data selectively without the storage provider learning the contents of the data or the words being searched for. Practical SSE schemes usually leak (sensitive) information during or after a query (e.g., the search pattern). Secure schemes on the other hand are not practical, namely they are neither efficient in the computational search complexity, nor scalable with large data sets. To achieve efficiency and security at the same time, we introduce the concept of distributed SSE (DSSE), which uses a query proxy in addition to the storage provider.\ud We give a construction that combines an inverted index approach (for efficiency) with scrambling functions used in private information retrieval (PIR) (for security). The proposed scheme, which is entirely based on XOR operations and pseudo-random functions, is efficient and does not leak the search pattern. For instance, a secure search in an index over one million documents and 500 keywords is executed in less than 1 second

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Heterogeneous Storage in HopsFS

In the recent years, the Apache Hadoop distributed file system (HDFS) has become increasingly popular for the storage of large data sets. Both the volume of the data and the variety of applications is unprecedented. The variety of tasks, each with its own access pattern and demands, calls for a file system that supports specialized storages for different tasks. This thesis describes the implementation of heterogeneous storage in HopsFS, a highly-available, highly-scalable version of HDFS. This makes the cluster aware of different storage types (e.g. hard disks and solid state drives) and allows users to specify preferred storage types for their data. By introducing new storage types, we build in support for storage technologies like SSDs and RAID. The latter is especially of interest, since it increases both bandwidth and reliability of the storage on individual nodes while continuing commodity hardware. Since network bandwidth is increasing orders of magnitude faster than disk bandwidth, increasing the disk throughput is of vital importance to avoid local storage becoming a bottleneck. The heterogeneous storage Application Programming Interface (API) described in this thesis offers HDFS administrators more control over their data while being compatible with the HDFS framework. Users can choose whether they want files stored on traditional disks, SSDs or more complex constructions using RAID and erasure coding

Heterogeneous Storage in HopsFS

In the recent years, the Apache Hadoop distributed file system (HDFS) has become increasingly popular for the storage of large data sets. Both the volume of the data and the variety of applications is unprecedented. The variety of tasks, each with its own access pattern and demands, calls for a file system that supports specialized storages for different tasks. This thesis describes the implementation of heterogeneous storage in HopsFS, a highly-available, highly-scalable version of HDFS. This makes the cluster aware of different storage types (e.g. hard disks and solid state drives) and allows users to specify preferred storage types for their data. By introducing new storage types, we build in support for storage technologies like SSDs and RAID. The latter is especially of interest, since it increases both bandwidth and reliability of the storage on individual nodes while continuing commodity hardware. Since network bandwidth is increasing orders of magnitude faster than disk bandwidth, increasing the disk throughput is of vital importance to avoid local storage becoming a bottleneck. The heterogeneous storage Application Programming Interface (API) described in this thesis offers HDFS administrators more control over their data while being compatible with the HDFS framework. Users can choose whether they want files stored on traditional disks, SSDs or more complex constructions using RAID and erasure coding

Colorectal liver metastases: surgery versus thermal ablation (COLLISION) – a phase III single-blind prospective randomized controlled trial

Abstract Background Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3 cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3 cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion If thermal ablation proves to be non-inferior in treating lesions ≤3 cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration NCT03088150, January 11th 2017

Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis. We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 ± 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically relevant mutated genes. In all cases, we found evidence for inactivation of TP53 and RB1 and identified recurrent mutations in the CREBBP, EP300 and MLL genes that encode histone modifiers. Furthermore, we observed mutations in PTEN, SLIT2 and EPHA7, as well as focal amplifications of the FGFR1 tyrosine kinase gene. Finally, we detected many of the alterations found in humans in SCLC tumors from Tp53 and Rb1 double knockout mice. Our study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background