Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Taking a Closer Look at Flight Crew Handling of Complex Failures: Ten Case Studies

Non-normal events, in particular system failures with serious operational impact are rare in flight operations. These events are not always easy to handle by flight crews. The aim of the performed study is to determine where in this process potential issues may lie. Ten incident reports are studied using a newly developed operational issue analysis framework. The framework is used to determine whether and how the current interfaces communicate the initial functional impact and functional impact delayed in time. Additionally, results from pilot interviews are presented which identified three phases of non-normal event handling: fault detection, fault management and strategic planning. Analysis of the ten cases shows that current alert systems are mainly supporting the first two phases while the strategic planning phase, requiring higher level functional information integrated into the operational context as well as failure impact later in time, is relying almost entirely on pilot knowledge and reasoning.Control & Simulatio

Solution-Space-based ATC support for 4DT heterogeneous aircraft-mix control

Future Air Traffic Management concepts will require air traffic controllers to move from a tactical to a strategic way of operation. This paper evaluates two novel concepts which support controllers to perform four-dimensional trajectory management in a contingency situation. The Travel Space Representation and Time-Space Diagram are both solution-space based displays where automation calculates all possible actions in real-time. All decision-making is still to be done by the operator but is greatly facilitated by this automation, as it shows all possible actions at a glance. An experiment is described which evaluated the performance of novice controllers in managing a sector where suddenly a bad weather cell emerged, requiring them to re-route traffic in space and time. Results show that the display concepts work well and support operators even in complex situations with a heterogeneous mix of aircraft types and speeds. Performance and workload indicators become worse for the higher-density, higher-heterogeneity situations.Control & Simulatio

The Effect of Synthetic Vision Enhancements on Landing Flare Performance

The usage of heads-down, non-conformal synthetic vision displays for landings below minimums has inherent problems during the flare due to minification effects. Literature showed that pilots can use four visual cues to perform a manual flare maneuver. Amongst their strategies, the Jacobson flare method seemed the most suitable to provide flare initiation and flare control cues. Offline, linear simulation results indicated that the Jacobson method was robust and its performance was comparable to an automatic landing system. An enhanced synthetic vision display was designed offering support cues to aid pilots with this landing method. An experiment was conducted in a fixed-based simulator with eight professional pilots and eight novice pilots. The enhanced display was tested against a basic version and conventional primary flight display with outside visuals. Each pilot group was split into two groups with different display orders to check for possible learning effects. The experiment showed that touchdown position was not affected by display type. The enhanced display did achieve softer touchdown sink rates compared to the basic version. The softest landings were done on outside visuals. A strong learning curve was also observed for the group of pilots that first flew with the enhanced display: this translated into better achieved performances with subsequent displays. Therefore, it could be a valuable tool for basic flight training and reduce the number of flight hours required in mastering the landing flare.Control & OperationsAerospace Engineerin

Learning for Air Traffic Management: guidelines for future AI systems

The SESAR-funded Modern ATM via Human / Automation Learning Optimisation (MAHALO) project recently completed two years of technical work exploring the human performance impacts of AI and Machine Learning (ML), as applied to enroute ATC conflict detection and resolution (CD&R). It first developed a hybrid ML CD&R capability, along with a realtime simulation platform and experimental User Interface. After a series of development trials, the project culminated in a pair of field studies (i.e., human-in-the-loop trials) across two EU countries, with a total of 35 operational air traffic controllers. In each of these two field studies, controller behaviour was first captured in a pre-test phase, and used to train the ML system. Subsequent main experiment trials then experimentally manipulated within controllers both Conformance (as either a personalised-, group average-, or optimized model) and Transparency (as ether a baseline vector depiction, an enhanced graphical diagram, or a diagram-plus-text presentation). The proposed paper presents guidelines on the design and implementation of ML systems in Air Traffic Control, derived from the results and lesson learned from the Simulations, as well as the qualitative feedback received from the controllers themselves.Control & Simulatio

Online Positioning of a Drone-Mounted Base Station in Emergency Scenarios

—Wireless communication networks provide a critical infrastructure, particularly in emergency situations due to disruptive events such as natural disasters or terrorist attacks. However, in these kinds of scenarios part of the network may no longer be operational and a traffic hotspot may emerge, which may result in coverage and/or capacity issues. Deploying self-steering drone-mounted base stations offers a potential method to quickly restore coverage and/or provide capacity relief in such situations, but appropriate positioning is crucial in order for a drone base station to be truly effective. Motivated by that challenge, we propose a data-driven algorithm to optimize the position of a drone base station in a scenario with a site failure and emergence of a traffic hotspot. We demonstrate that the use of a drone, when properly positioned, yields significant performance gains, and that our algorithm outperforms benchmark mechanisms in a wide range of scenarios. In addition, we show that our algorithm is able to find a near-optimal position for the drone in a reasonable amount of time, and even has the ability to track the optimal position in case of a moving hotspot.Network Architectures and Service

Drone-Assisted Cellular Networks: Optimal Positioning and Load Management

The use of drone base stations offers an agile mechanism to safeguard coverage and provide capacity relief when cellular networks are under stress. Such stress conditions can occur for example in case of special events with massive crowds or network outages. In this paper we focus on a disaster scenario with emergence of a hotspot, and analyze the impact of the drone position (altitude, horizontal position) and selection bias on the network performance. We determine the optimal settings of these control parameters as a function of the hotspot location, and demonstrate that the optimized values can drastically reduce the fraction of failed calls.Network Architectures and Service

A passive heat tracer experiment to determine the seasonal variation in residence times in a managed aquifer recharge system with DTS

Targeted provisional session N°8.01 The seasonal variation in residence times is determined in a managed aquifer recharge system using a passive heat tracer test. The managed aquifer recharge system consists of a sequence of alternating elongated recharge basins and rows of recovery wells. The temperature of both the water in the recharge basin and the surface influence the temperature in the aquifer. The flow field changes when the temperature changes, as the hydraulic conductivity is a function of the temperature. Fiber optic cables were inserted up to a depth of 20 meters with direct push equipment to measure vertical temperature profiles with DTS. In this fashion, the fiber optic cables are in direct contact with the aquifer and the disturbance of the aquifer is minimal. The measured spatial and temporal temperature variations in the subsurface were modeled with SEAWAT, a coupled flow and heat transport model. MODPATH was used to compute flow paths and residence times. During the winter, a larger fraction of the water moves through the warmer lower part of the aquifer, thereby increasing the residence time. The opposite happens during the summer, when most of the water moves through the warmer upper part of the aquifer, resulting in shorter residence times.Water Resource

Bishop Fulton J. Sheen: America’s public critic of psychoanalysis, 1947–1957

This paper examines the role of Bishop Fulton Sheen in the popularization of Freudian psychoanalysis in the United States during the 1940s and 50s. Social historians argue that Freudian ideas were pervasive in American culture during this period. While their claim speaks mainly to the impact of psychoanalysis on the cultural elite and college educated, they also suggest that Freudian ideas affected ordinary men and women. In the former case, the group impacted is small and not representative of the population as a whole; in the latter, the evidence is sparse and impressionistic. Neglected in their consideration is the influence of Fulton Sheen whose opinions on Freud reached an audience of 30,000,000 during the height of the popularity of his TV show, Life is Worth Living. Sheen\u27s audience was more inclusive and representative of mainstream America. The negative and highly cautionary view of psychoanalysis he presented to many Americans was contrary to that which was promoted to and embraced by many of the college educated and likely shaped both their views of Freud and psychoanalytic therapy