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

Ecological Approach to Pilot Terrain Awareness

The upgrade of the flight deck instruments from electro-mechanical dials and gauges towards computer-driven systems and interfaces was a necessary step to accommodate the increasing demands in flight technical performance and safety. The upgrade was a relatively slow process, however, where new systems were developed and installed as soon as the technology was available. As a result, many systems are not always well integrated in terms of presenting information. Together with the increasing amount of automation, the flight deck has become prone to issues such as information ambiguities and misunderstandings between the pilot and the (automated) avionic systems. This phenomenon is commonly labeled as a lack of "situation awareness" (SA) and has become a new cause for accidents. That is, pilots are unaware sometimes of the current flight situation, a situation that in itself may be caused by the automation. A recent example of this phenomenon is the Turkish Airlines accident near Schiphol on February 25 2009. The focus of this thesis is on aircraft terrain avionics, such as the Terrain Awareness Warning System (TAWS) and the Synthetic Vision System (SVS), that form a typical illustration of the evolution process and its issue regarding SA. The work in this thesis aimed to identify and address the missing information that would span the information gaps between the SVS and the TAWS to benefit pilot SA. The Ecological Interface Design (EID) framework was explored to accomplish this goal. EID was originally developed for the process industry (like nuclear power plants) and is therefore a rather novel approach in the field of flight deck design. The results of experimental evaluations indicated that pilots managed to benefit from the ecological interface enhancements to successfully and safely deal with hazardous terrain conflicts, even when encountering unanticipated events. It was found that the ecological interfaces made pilots more aware of the aircraft capabilities and much more actively involved in the decision-making loop to prevent fatal mishaps.Control and SimulationAerospace Engineerin

Future avionics for small aircraft; towards safer persionalized air transportation

Aerospace Engineerin

Air traffic controller decision-making consistency and consensus in conflict solution performance

Consistency and consensus in conflict solution performance was investigated in two real-time simulations involving experienced air traffic controllers and trainees. The simulations consisted of participants repeatedly playing a specific en route traffic scenario. Conflict solution performance and consistency was measured by analysing participant’s solutions to a specifically designed conflict. Consensus was determined by comparing participant’s consistent conflict solution behaviour. Four different clusters of consistent behaviour were identified. All participants could be classified as consistent according to one or more of these clusters. Consensus in solving the designed conflict could not be determined between participants. There were, however, smaller groups of participants who solved the designed conflict similarly. Participants varied considerably in terms if when to interact and solve the conflict. This is a potential issue when it comes to determining thresholds for the timing of decision-aid interaction.Control & OperationsAerospace Engineerin

Context-dependent ATC complexity metric

Several studies have investigated Air Traffic Control (ATC) complexity metrics in a search for a metric that could best capture workload. These studies have shown how daunting the search for a universal workload metric (one that could be applied in different contexts: sectors, traffic patterns, controllers, or ATC tasks) can be. We propose that complexity metrics should be tailor made to the task they were meant to be used for, and focus in the elicitation of parameters that could best capture complexity of the task at hand. For the ATC task of rerouting aircraft a selection of relevant context parameters was made, and based on these a new complexity metric called SSD Composite is proposed. The metric is based on the Solution Space Diagram (SSD) concept. As a pilot study, a low fidelity simulation in which ATM experts operated as controllers and provided self assessments of workload was conducted. Data obtained from the simulation runs was used to compare traditional metrics (Traffic Load and NASA/FAA’s Dynamic Density) against the SSD Composite metric by means of mixed-effects linear regressions. Results showed that SSD-based metrics were much less sensitive to sector or traffic pattern effects and that the amount of observed workload variation accounted for by the SSD Composite fixed effects was higher than that of the Dynamic Density metric.Control and OperationsAerospace Engineerin

Investigation of Practical Flight Envelope Protection Systems for Small Aircraft

Personal air transportation utilizing small aircraft is a market that is expected to grow significantly in the future. For this segment, “stick and rudder” related accidents should be mitigated to guide this process in a safe manner. Instead of downscaling advanced and expensive fly-by-wire platforms that incorporate flight envelope protection found in commercial aircraft, a low cost solution should be considered. This paper focuses on a flight envelope protection system for small aircraft, to allow carefree maneuvering for the less experienced pilot. Preliminary results are obtained from an empirical comparison study in the time domain, between a PID based control limiting approach, a command limiting approach and a constrained Flight Control Law (FCL) approach using Model-based Predictive Control (MPC), with and without parametric model uncertainties. Investigation of the results reveals that, for this study, command limiting and MPC should be preferred over control limiting and that the practicality of command limiting outweighs the small performance increase of MPC.Control & OperationsAerospace Engineerin

Situation Awareness Prompts: Bridging the Gap between Supervisory and Manual Air Traffic Control

To meet increasing safety and performance demands in air traffic control (ATC), more advanced automated systems will be introduced to assist human air traffic controllers. Some even foresee complete automation, with the human as a supervisor only to step-in when automation fails. Literature and empirical evidence suggest that supervising highly-automated systems can cause severe vigilance and complacency problems, out-of-the-loop situation awareness and transient workload peaks. These impair the ability for humans to successfully take over control. In this study, situation awareness prompts were used as a way to keep controllers cognitively engaged during their supervision of a fully automated ATC system. Results from an exploratory human-in-the-loop experiment, in which eight participants were instructed to monitor a fully automated ATC system in a simplified ATC context, show a significant decrease in workload peaks following an automation failure after being exposed to high-level SA questions. Although the selected method did not necessarily yield improved safety and manual control efficiency, results suggest that using situation awareness feedback in line with controllers' attention could be an avenue worth exploring further as a training tool.Control & Simulatio

An Avionics Touch Screen based Control Display Concept

In many cockpits, control display units (CDUs) are vital input and information devices. In order to improve the usability of these devices, Barco, in cooperation with TU-Delft, created a touch screen control unit (TSCU), consisting of a high-quality multi-touch screen. The unit fits in the standard dimensions of a conventional CDU and is thus suitable for both retrofit and new installations. The TSCU offers two major advantages. First, the interface can be reconfigured to enable consecutive execution of several tasks on the same display area, allowing for a more efficient usage of the limited display real-estate as well as a potential reduction of cost. Secondly, advanced graphical interface design, in combination with multi-touch gestures, can improve human-machine interaction. To demonstrate the capabilities of this concept, a graphical software application was developed to perform the same operations as a conventional CDU, but now using a direct manipulation interface (DMI) of the displayed graphics. The TSCU can still be used in a legacy CDU mode, displaying a virtual keyboard operated with the touch interface. In addition, the TSCU could be used for a variety of other cockpit functions. The paper concludes with a report of pilot and non-pilot feedback.Control and OperationsAerospace Engineerin

Human Performance in Solving Multi-UAV Over-Constrained Dynamic Vehicle Routing Problems

For many logistics applications, such as drone delivery missions, finding an optimized network of routes yields a Vehicle Routing Problem (VRP). Such optimizations are mostly conducted offline prior to actual operations for reasons of computational complexity. In case disturbances arise during operations, for example a sudden loss of a vehicle, the VRP needs to be re-optimized in real-time and this raises concerns regarding obtaining a solution within time. In a previous study, it was demonstrated that humans, when supported through a human-machine interface, can quickly deal with these routing problems through satisficing, providing workable solutions. This paper extends our previous research by exposing human operators to an over-constrained VRP with different mission priorities and vehicle capabilities. Experiment results (n = 16) indicate that the mission type had the largest impact on how participants used the interface and what constraints were relaxed. In particular, during a search-and-rescue context the mission emphasis was put on delivering (medical) payload (close) to as many customers as possible, even if this would involve sacrificing vehicles and relaxing the depot constraint. Ethical aspects of the VRP are taken into account which algorithms do not by themselves, underlining the importance of involving humans in automation. Human operators complement algorithms with their context awareness, yielding more safe, resilient and responsible systems.Control & Simulatio

Evaluation of a 3D Solution Space-based ATC Workload Metric

Air Traffic Control (ATC) workload is a limiting factor for air traffic growth, creating a need for objective ATC workload metrics. Previous research has shown that the solution space diagram can be a basis for a workload prediction metric. The current solution space metric however, does not incorporate altitude. In this paper, a 3D solution space metric is described and evaluated. An experiment has been conducted to test the relation of the 3D solution space metric with workload and compare it to other workload metrics; the aircraft count, and a quasi-3D metric: the 2D layered solution space and the Instantaneous Self Assessment-based method. Weak correlations with workload were found for all tested metrics and no significant differences were found between them. Although no significant differences were found, the 2D layered metric showed better results than the 3D solution space-based metric, indicating that air traffic controllers might think in 2D layers over fixed altitude ranges rather than considering the complete 3D physical solution space.Control & Simulatio