11 research outputs found
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Optimal inspection and maintenance for stochastically deteriorating systems
This thesis concerns the optimisation of maintenance and inspection for stochastically deteriorating systems. The motivation for this thesis is the problem of determining condition based maintenance policies, for systems whose degradation may be modelled by a continuous time stochastic process. Our emphasis is mainly on using the information gained from inspecting the degradation to determine efficient maintenance and inspection policies. The system we shall consider is one in which the degradation is modelled by a Levy process, and in which failure is defined to occur when the degradation reaches a critical level. It is assumed that the system may be inspected or repaired at any time, and that the costs of inspections and repairs may depend on the level of system degradation. Initially we look at determining optimal inspection policies for systems whose degradation may be directly and perfectly observed, before extending this analysis to the case where the degradation is unobservable, and a related covariate process is used to determine maintenance decisions. In both cases it is assumed the replacement policy is fixed and known in advance. Finally we consider the case of joint optimisation of maintenance and inspection, for cases in which the maintenance action has either deterministic or random effect on the degradation level. In all of these cases we use the properties of the Levy process degradation model to form a recursive relationship which allows us to determine integral and functional equations for the maintenance cost of the system. Solutions to these determine optimal periodic and non-periodic inspection and maintenance policies. Throughout the thesis we use the gamma process degradation model as an example. For this model we determine optimal perfect inspection policies for the cases when inspections are periodic and non-periodic. As a special case of a covariate process we consider the optimal imperfect periodic inspection policy. Finally we obtain jointly optimal deterministic-maintenance and periodic-inspection policies
Effect of acute hyperoxia on the bronchodilator response to salbutamol in stable asthmatic patients.
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. 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; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes