Health state utility values (QALY weights) for Huntington's disease: an analysis of data from the European Huntington's Disease Network (EHDN)

Huntington's Disease (HD) is a hereditary neurodegenerative disorder which affects individuals' ability to walk, talk, think, and reason. Onset is usually in the forties, there are no therapies currently available that alter disease course, and life expectancy is 10-20 years from diagnosis. The gene causing HD is fully penetrant, with a 50% probability of passing the disease to offspring. Although the impacts of HD are substantial, there has been little report of the quality of life of people with the condition in a manner that can be used in economic evaluations of treatments for HD. Health state utility values (HSUVs), used to calculate quality-adjusted life-years (QALYs), are the metric commonly used to inform such healthcare policy decision-making.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site.Publishe

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

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

De leegte als bouwsteen

A+UUrbanism, ArchitectureArchitectur

System ID Modern Control Algorithms for Active Aerodynamic Load Control and Impact on Gearbox Loading

Prior work on active aerodynamic load control (AALC) of wind turbine blades has demonstrated that appropriate use of this technology has the potential to yield significant reductions in blade loads, leading to a decrease in wind cost of energy. While the general concept of AALC is usually discussed in the context of multiple sensors and active control devices (such as flaps) distributed over the length of the blade, most work to date has been limited to consideration of a single control device per blade with very basic Proportional Derivative controllers, due to limitations in the aeroservoelastic codes used to perform turbine simulations. This work utilizes a new aeroservoelastic code developed at Delft University of Technology to model the NREL/Upwind 5 MW wind turbine to investigate the relative advantage of utilizing multiple-device AALC. System identification techniques are used to identify the frequencies and shapes of turbine vibration modes, and these are used with modern control techniques to develop both Single-Input Single-Output (SISO) and Multiple-Input Multiple-Output (MIMO) LQR flap controllers. Comparison of simulation results with these controllers shows that the MIMO controller does yield some improvement over the SISO controller in fatigue load reduction, but additional improvement is possible with further refinement. In addition, a preliminary investigation shows that AALC has the potential to reduce off-axis gearbox loads, leading to reduced gearbox bearing fatigue damage and improved lifetimes.Aerodynamics & Wind EnergyAerospace Engineerin

Nieuwe Perspectieven voor verstedelijkte delta's

UrbanismArchitecture and The Built Environmen

On a Combinatorial Conjecture Concerning Disjoint Occurrences of Events

Recently van den Berg and Kesten have obtained a correlation-like inequality for Bernoulli sequences. This inequality, which goes in the opposite direction of the FKG inequality, states that the probability that two monotone (i.e., increasing or decreasing) events "occur disjointly" is smaller than the product of the individual probabilities. They conjecture that the monotonicity condition is immaterial, i.e., that the inequality holds for all events. In the present paper we try to make clear the intuitive meaning of the conjecture and prove some nontrivial special cases, one of which, a pure correlation inequality, is an extension of Harris' FKG inequality.Electrical Engineering, Mathematics and Computer Scienc

Analyzing Inverse Infrastructures using a Complex Adaptive Systems Perspective

The number of inverse infrastructures (Vree, 2003), that is, user-driven and self-organizing infrastructures, is rising and unsettling policies that are foremost tailored to deal with large-scale and centrally-governed infrastructures (Egyedi et al. 2012). To better understand and address this mismatch, Van den Berg (2012) has developed a complex adaptive systems (CAS) framework for analyzing inverse infrastructures. It is based on and well-fits CASs in physics, mathematics and biology. In this paper we explore the framework’s applicability to three inverse infrastructures, i.e.: Wikipedia (Davis and Nikolic, 2012), citizen-driven waste paper collection (De Jong and Mulder, 2012), and the user-driven roll-out of local glass fiber networks (Weijers, 2012; Nederkoorn, 2012). Applying it reveals that, while the framework’s most basic elements can be identified rather straightforwardly, other elements are often more difficult to identify in human CASs. Our tentative conclusion is that (i) the framework is a good starting point for analyzing inverse infrastructures, and (ii) more case studies are needed to fully understand the conditions under which self-organized emergent behavior of complex infrastructures can be observed.Infrastructures, Systems and ServicesTechnology, Policy and Managemen

Wat maakt cyber security anders dan informatiebeveiliging?

De termen “informatiebeveiliging” en “cyber security” worden vaak door elkaar gebruikt soms met dezelfde, soms met een afwijkende betekenis. Velen spreken vandaag de dag ook over cyberspace, bijvoorbeeld als een nieuw (door de mens gecreëerd) vijfde domein naast de bestaande domeinen land, water, lucht en ruimte. Een en ander roept de vraag op of informatiebeveiliging en cyber security (wel of niet) fundamenteel van elkaar verschillen. Geconfronteerd met de uitdaging om nieuw multidisciplinair onderzoek & onderwijs rond cyber security te ontwikkelen, ontstond de noodzaak om orde op zaken te stellen en de begrippen helder ten opzichte van elkaar te positioneren. Dit heeft geleid tot een nieuwe conceptualisatie rond de begrippen cyberspace en cyber security. Informatiebeveiliging is in deze visie onderdeel van het bredere begrip van cyber security. De eerste ervaringen rond het gebruik van dit nieuwe begrippenkader zijn zeer positief.Engineering, Systems and ServicesTechnology, Policy and Managemen

Grasping cybersecurity: A set of essential mental models

For most people, cybersecurity is a hard to grasp notion. Traditionally, cybersecurity has been considered as a technical challenge and still many specialists view it equivalent with information security, with the notions of confidentiality, integrity and availability as starting points of thinking. And although others searched for a broader perspective, the complexity and ambiguity of the notion still thwarts a common understanding. While developing and executing a MSc cybersecurity program for professionals, the lack of a common understanding of what cybersecurity entails was again observed. Stimulated by this, we started to look for and define a new, transdisciplinary conceptualization of cybersecurity that everyone can agree upon. It resulted in two scientific papers published. This paper describes the outcomes of the continuation of our research journey. It turned out that the earlier introduced description of two key notions, namely that of cyberspace and that of cybersecurity, can still be considered as adequate starting points. Here, we describe a set of additional mental models that elaborates them and provides more detail to the meaning of the two key notions. In practice, it turned out that the additional mental models strongly support the description and analysis of existing and upcoming cybersecurity challenges and helps to understand how everybody, in his or her various roles, can or should contribute to reducing the related cyber risks to adequate levels. We further discovered that for certain cybersecurity challenges, especially those related to efficient cyber risk mitigation, we could not yet identify an adequate sub-set of mental models. This defines the agenda for near future cybersecurity research.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Information and Communication Technolog