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

Discuss Inter-Organization Coordination by Transaction Cost Theory–The Case of Taiwan Yacht Hardware Accessories Supplier Industry

[[abstract]]全球化的競爭環境，台灣企業正面臨快速變遷的市場改變，而船舶零件產業漸漸走向客製化、樣式多、出貨迅速、出貨數量少、品質優良及價格合理，為了適應潮流，企業不得已一直改變經營模式去反應客戶需求，企業核心競爭力是企業的核心價值，提升核心競爭力才是企業生存的根本之道。台灣早期素稱是遊艇王國，船舶零配件產業是供應造船業的根本，帆船係屬遊艇產業的一部分，而台灣船舶零配件產業在中國大陸、韓國及其他新興國家的經濟崛起下如何在國際競爭中生存？本研究認為須透過供應鏈跨組織合作來進行產業整合，已持續提升競爭優勢。企業間的跨組織合作除了能連接企業的互動和整合，也加強協助企業達成經營擴大市場占有率的管理目標。本研究根據交易成本理論分析帆船零配件產業各科跨組織合作時的資產專屬性、投機行為、環境不確定因素與搜尋成本間的相互關係。 本研究目的為: 一、 跨組織合作中，進行跨組織合作的企業，有何種特性？ 二、 這些特性對跨組織合作的傾向為何？ 三、 供應鏈跨組織合作廠商的特性和傾向可供台灣船舶帆船零件產業有何參考依據? 研究發現，如欲開發產品，而產品的資產專屬性越高時，企業越可能會採取自行營運；且企業跨組織合作時呈現的投機行為皆低；環境不確定越高時，企業越有可能採取自行營運；有些產品需投入大量的人力與財力去取得機械設備、生產流程及培訓人才，成本相對提升許多，在此情況下，廠商會採取供應鏈跨組織合作來減少搜尋的成本。[[abstract]]With the rapid changes of globalized competition，Taiwan industries are facing with strengthen competitiveness from the same competitors.Each company needs to integrate all the resources with great effort and to ensure that the process of producing model or cooperate business model is improved .How to be the winner in the competitors is a good question for each manager.This thesis will discuss about increasing core competence by inter-organization coordination.by〝Core Competence is the core value of the company`s business model〞,we know to increase the company core competence is the only way to survive.Company is not only needs to quickly upgrade and change business model to respond the customer`s demand but also needs to stabilize the model of cooperate companies by inter-organization coordination. For years,Taiwan is the leader of shipyard industry in the world.Yacht-parts or hardware accessories are the basic foundations to supply shipyard industry.No doubt that small boats like dinghy、OP、laser or hobie cat are also the part of shipyard industry.Do the yacht-parts suppliers in Taiwan have any condition to survive in competitors from the world？In this study,the inter-organization coordination can not only strengthen the connection between different manufacturers but also share the resources each other to achieve increasing market share.Base on the thesis by Williamson (1975) of Asset Specificity、Opportunistic Behavior、Uncertainty and Searching Cost.The study will analyze inter-organization coordination and the factors which affect mutual collaboration of inter-organization. The purposes of the study are: 1. Discuss the process of the cross-organizational coordination in different Taiwan yacht-parts suppliers. 2. Propose the factors of affecting inter-organization coordination in Taiwan yacht-parts suppliers,based on the transaction cost theories. 3. What references are given for the managers？ The results reveal that it has the positive relationship between the value of manufacturer and running cost of the company.The more value the manufacturer has,the more core capacity the manufacturer has.[[note]]碩

Unique clinical characteristics and SCN5A mutations in patients with Brugada syndrome in Taiwan

Brugada syndrome (BrS) is a hereditable sudden cardiac death (SCD). Mutations in the SCN5A gene (the most common BrS-causing gene) are responsible for 20–25% of this disease in Caucasian populations. However, the prevalence of SCN5A mutations in patients with BrS in the Chinese Han population in Taiwan remains unknown. Therefore, in this study, we investigated the prevalence of the SCN5A mutation in the largest BrS cohort in Taiwan. Methods: We consecutively enrolled 47 unrelated patients with BrS from medical centers and hospitals in Taiwan between 2000 and 2010. Mutations within all the 27 translated exons, and exon–intron boundaries of the SCN5A-encoded cardiac sodium channel were screened in all patients with BrS using direct sequencing. A total of 500 unrelated healthy volunteers with a normal electrocardiogram were genotyped as a control group. Results: SCN5A genetic variants were identified in 14 of the 47 patients with BrS and four of the 14 patients with BrS had missense mutations (1651 G>A, 1776 C>G, 3578 G>A). The prevalence rate of SCN5A mutations was approximately 8% (4/47), which was significantly lower than that reported in Caucasian populations (20–25%; p = 0.0007). The average age of these 14 BrS patients with SCN5A variants at diagnosis (12 men and 2 women) was 40 ± 13 years. Four patients experienced SCD, and six presented with seizure or syncope. Only three patients (3/14, 21.4%) had a family history of SCD. Conclusion: The prevalence of SCN5A mutations in the Chinese Han population in Taiwan may be lower than that reported in the Caucasian populations. In addition, most patients with BrS did not have a family history of SCD

2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the management of atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia. Both the incidence and prevalence of AF are increasing, and the burden of AF is becoming huge. Many innovative advances have emerged in the past decade for the diagnosis and management of AF, including a new scoring system for the prediction of stroke and bleeding events, the introduction of non-vitamin K antagonist oral anticoagulants and their special benefits in Asians, new rhythm- and rate-control concepts, optimal endpoints of rate control, upstream therapy, life-style modification to prevent AF recurrence, and new ablation techniques. The Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology aimed to update the information and have appointed a jointed writing committee for new AF guidelines. The writing committee members comprehensively reviewed and summarized the literature, and completed the 2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the Management of Atrial Fibrillation. This guideline presents the details of the updated recommendations, along with their background and rationale, focusing on data unique for Asians. The guidelines are not mandatory, and members of the writing committee fully realize that treatment of AF should be individualized. The physician's decision remains most important in AF management