108 research outputs found

    On the Schoenberg Transformations in Data Analysis: Theory and Illustrations

    Get PDF
    The class of Schoenberg transformations, embedding Euclidean distances into higher dimensional Euclidean spaces, is presented, and derived from theorems on positive definite and conditionally negative definite matrices. Original results on the arc lengths, angles and curvature of the transformations are proposed, and visualized on artificial data sets by classical multidimensional scaling. A simple distance-based discriminant algorithm illustrates the theory, intimately connected to the Gaussian kernels of Machine Learning

    Termination of the leprosy isolation policy in the US and Japan : Science, policy changes, and the garbage can model

    Get PDF
    BACKGROUND: In both the US and Japan, the patient isolation policy for leprosy /Hansen's disease (HD) was preserved along with the isolation facilities, long after it had been proven to be scientifically unnecessary. This delayed policy termination caused a deprivation of civil liberties of the involuntarily confined patients, the fostering of social stigmas attached to the disease, and an inefficient use of health resources. This article seeks to elucidate the political process which hindered timely policy changes congruent with scientific advances. METHODS: Examination of historical materials, supplemented by personal interviews. The role that science played in the process of policy making was scrutinized with particular reference to the Garbage Can model. RESULTS: From the vantage of history, science remained instrumental in all period in the sense that it was not the primary objective for which policy change was discussed or intended, nor was it the principal driving force for policy change. When the argument arose, scientific arguments were employed to justify the patient isolation policy. However, in the early post-WWII period, issues were foregrounded and agendas were set as the inadvertent result of administrative reforms. Subsequently, scientific developments were more or less ignored due to concern about adverse policy outcomes. Finally, in the 1980s and 1990s, scientific arguments were used instrumentally to argue against isolation and for the termination of residential care. CONCLUSION: Contrary to public expectations, health policy is not always rational and scientifically justified. In the process of policy making, the role of science can be limited and instrumental. Policy change may require the opening of policy windows, as a result of convergence of the problem, policy, and political streams, by effective exercise of leadership. Scientists and policymakers should be attentive enough to the political context of policies

    Pan-cancer analysis of whole genomes

    Get PDF
    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
    • 

    corecore