Koostööäriprotsesside läbiviimine plokiahelal: süsteem

Tänapäeval peavad organisatsioonid tegema omavahel koostööd, et kasutada ära üksteise täiendavaid võimekusi ning seeläbi pakkuda oma klientidele parimaid tooteid ja teenuseid. Selleks peavad organisatsioonid juhtima äriprotsesse, mis ületavad nende organisatsioonilisi piire. Selliseid protsesse nimetatakse koostööäriprotsessideks. Üks peamisi takistusi koostööäriprotsesside elluviimisel on osapooltevahelise usalduse puudumine. Plokiahel loob detsentraliseeritud pearaamatu, mida ei saa võltsida ning mis toetab nutikate lepingute täitmist. Nii on võimalik teha koostööd ebausaldusväärsete osapoolte vahel ilma kesksele asutusele tuginemata. Paraku on aga äriprotsesside läbiviimine selliseid madala taseme plokiahela elemente kasutades tülikas, veaohtlik ja erioskusi nõudev. Seevastu juba väljakujunenud äriprotsesside juhtimissüsteemid (Business Process Management System – BPMS) pakuvad käepäraseid abstraheeringuid protsessidele orienteeritud rakenduste kiireks arendamiseks. Käesolev doktoritöö käsitleb koostööäriprotsesside automatiseeritud läbiviimist plokiahela tehnoloogiat kasutades, kombineerides traditsioonliste BPMS- ide arendusvõimalused plokiahelast tuleneva suurendatud usaldusega. Samuti käsitleb antud doktoritöö küsimust, kuidas pakkuda tuge olukordades, milles uued osapooled võivad jooksvalt protsessiga liituda, mistõttu on vajalik tagada paindlikkus äriprotsessi marsruutimisloogika muutmise osas. Doktoritöö uurib tarkvaraarhitektuurilisi lähenemisviise ja modelleerimise kontseptsioone, pakkudes välja disainipõhimõtteid ja nõudeid, mida rakendatakse uudsel plokiahela baasil loodud äriprotsessi juhtimissüsteemil CATERPILLAR. CATERPILLAR-i süsteem toetab kahte lähenemist plokiahelal põhinevate protsesside rakendamiseks, läbiviimiseks ja seireks: kompileeritud ja tõlgendatatud. Samuti toetab see kahte kontrollitud paindlikkuse mehhanismi, mille abil saavad protsessis osalejad ühiselt otsustada, kuidas protsessi selle täitmise ajal uuendada ning anda ja eemaldada osaliste juurdepääsuõigusi.Nowadays, organizations are pressed to collaborate in order to take advantage of their complementary capabilities and to provide best-of-breed products and services to their customers. To do so, organizations need to manage business processes that span beyond their organizational boundaries. Such processes are called collaborative business processes. One of the main roadblocks to implementing collaborative business processes is the lack of trust between the participants. Blockchain provides a decentralized ledger that cannot be tamper with, that supports the execution of programs called smart contracts. These features allow executing collaborative processes between untrusted parties and without relying on a central authority. However, implementing collaborative business processes in blockchain can be cumbersome, error-prone and requires specialized skills. In contrast, established Business Process Management Systems (BPMSs) provide convenient abstractions for rapid development of process-oriented applications. This thesis addresses the problem of automating the execution of collaborative business processes on top of blockchain technology in a way that takes advantage of the trust-enhancing capabilities of this technology while offering the development convenience of traditional BPMSs. The thesis also addresses the question of how to support scenarios in which new parties may be onboarded at runtime, and in which parties need to have the flexibility to change the default routing logic of the business process. We explore architectural approaches and modelling concepts, formulating design principles and requirements that are implemented in a novel blockchain-based BPMS named CATERPILLAR. The CATERPILLAR system supports two methods to implement, execute and monitor blockchain-based processes: compiled and interpreted. It also supports two mechanisms for controlled flexibility; i.e., participants can collectively decide on updating the process during its execution as well as granting and revoking access to parties.https://www.ester.ee/record=b536494

Next Generation of Genotype Imputation Methods

In the past several years, we have witnessed numerous human genetic studies that have systematically evaluated the contribution of genetic polymorphisms to various complex diseases, and enabled the evolution of multiple treatment strategies, particularly pharmaceutical therapies. Genotype imputation has been a key step in such studies - increasing the power of gene mapping analyses, facilitating harmonization of results across studies, and accelerating fine-mapping efforts. Imputation requires access to a reference panel of densely sequenced genomes and is a computationally intensive process, even with modern high performance computing. Furthermore, reference panels often have data privacy issues that inhibit users from having direct access to the data. The goal of this dissertation is to design novel strategies to address these challenges for the next generation of imputation methods. In the first project, I describe our efforts to create a reference panel of ~32,000 individuals with ~40M variants by combining genetic information obtained across 20 whole genome sequencing studies (Haplotype Reference Consortium). In the second project, I describe a novel idea called ‘state space reduction’ that reduces computational requirements of genotype imputation by orders of magnitude without any loss of accuracy (minimac3). I also present a web-based platform for imputation that greatly improves user experience and productivity. In the third project, I extend the idea of state space reduction by implementing a more complex version of the strategy that produces additional cost savings (minimac4). In the fourth project, I introduce the idea of meta-imputation: a novel approach that integrates imputed data from multiple reference panels at overlapping sites without interfering in the imputation algorithm (MetaMinimac). In summary, the purpose of this dissertation research is to develop statistical methods and computational tools that will benefit other researchers in the next generation of human gene mapping studies. These imputation tools will detect rare variants with higher accuracy, consequently increasing the power of association studies.PHDBiostatisticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/138466/1/sayantan_1.pd

Digital health and cardiovascular healthcare professionals in Portugal: current status, expectations and barriers to implementation

Introdução e objetivos A saúde digital é um conceito amplo, que junta a tecnologia aos cuidados de saúde, desempenhando um papel cada vez mais importante na prática clínica diária dos profissionais de saúde e promissor na prevenção e tratamento de doenças cardiovasculares. Não existem dados consistentes que avaliem a posição dos profissionais de saúde portugueses em relação à implementação da saúde digital na medicina cardiovascular. Por conseguinte, este estudo nacional transversal visa compreender o panorama geral da implementação da saúde digital na rotina diária dos profissionais de saúde cardiovascular em Portugal e identificar tanto as expectativas como os obstáculos à sua adoção. Métodos Um inquérito de 18 perguntas foi construído para as necessidades específicas deste estudo e distribuído a 1174 potenciais respondedores da mailing list da Sociedade Portuguesa de Cardiologia. Resultados Foram obtidas 117 respostas válidas (taxa de resposta ao inquérito de 10%). Quase todos os respondedores tinham um smartphone e um computador portátil e dois terços tinham um tablet. Os sistemas eletrónicos de informação médica foram a ferramenta mais utilizada (84% dos inquiridos) e considerada a mais relevante para melhorar os cuidados de saúde cardiovasculares. Mais de 2 em 3 dos inquiridos relataram utilizar tecnologias implantáveis (sensores ou dispositivos), telemedicina e as redes sociais e todas estas ferramentas foram consideradas "muito relevantes" ou "totalmente relevantes" pela maioria. A maior parte dos respondedores demonstrou expectativas positivas relativamente ao impacto da saúde digital na medicina cardiovascular: 78% concordaram que esta pode melhorar os outcomes em saúde, 64% que promove a literacia em saúde e 63% que pode diminuir os custos dos cuidados de saúde. A incapacidade dos pacientes em utilizar smartphones, o acesso limitado a dispositivos eletrónicos e a falta de regulamentação legal da saúde digital foram as barreiras mais cotadas. Conclusão Globalmente, a maioria dos profissionais de saúde cardiovascular em Portugal tinham pelo menos três dispositivos eletrónicos (principalmente smartphones, computadores portáteis e tablet) e mostraram expectativas positivas relativamente ao impacto atual e futuro da saúde digital na medicina cardiovascular. A literacia e a adoção de tecnologia relacionada com a saúde digital pelos pacientes, bem como a falta regulamentação jurídica, foram identificados como os obstáculos mais importantes para aumentar a adoção de ferramentas de saúde digital na medicina cardiovascular.Introduction and objectives: Digital health (DH) is a broad concept, bringing together technology and healthcare, that is playing an increasingly important role in the daily routine of healthcare professionals and promising to contribute to the prevention and treatment of cardiovascular diseases. There is no solid data evaluating the position of Portuguese healthcare professionals (HCP) towards the implementation of DH in cardiovascular medicine. Therefore, this national cross-sectional study aims to provide a snapshot of DH's implementation in the Portuguese cardiovascular HCP routine and identify both expectations and barriers to its adoption. Methods: An 18-question survey was created for the specific needs of this study and distributed to 1174 potential receivers of the Portuguese Society of Cardiology mailing list. Results: We collected 117 valid responses (survey response rate of 10%). Almost all participants had smartphones and laptops, and two-thirds had tablets. Electronic medical information systems were the most used DH tool (84% of respondents) and were considered the most relevant in improving cardiovascular care. Implantable technologies (sensors or devices), telemedicine and social media were also used by more than 2 out of 3 respondents and considered "very relevant" or "totally relevant" by most of them. Most participants showed positive expectations regarding the impact of DH in cardiovascular medicine: 78% agreed that DH might improve health outcomes, 64% that it promotes health literacy and 63% that it may decrease healthcare costs. The top-rated barriers were patients' inability to use smartphones, limited access to electronic devices, and lack of legal regulation of DH. Conclusion: Most Portuguese cardiovascular HCP had at least three electronic devices (primarily smartphones, laptops and tablets) and showed positive expectations regarding DH's current and future impact on cardiovascular medicine. Patient DH literacy, technology adoption, and DH regulation were identified as the most important blockers to increasing the adoption of DH tools in cardiovascular medicine

State management in coreless mobile networks

The number of mobile Internet users has skyrocketed and with the advent of the Internet of things we are reaching the limits of the current telecommunications standard 4G. The improvements and goals set for the next standard, 5G, are not trivial and research is in progress to reach them. Improvements across all involved technology fields is needed. In this thesis we present a novel mobile network architecture-coreless mobile networks- and develop state management concepts, which we base on the analysis of the current 4G/LTE architecture. The coreless mobile network focuses on the redesign of the state management in mobile networks, more precisely, removal of state from 4G core network entities into an eternal ubiquitous data store. The architecture follows trends in current research, particularly network function virtualisation, software defined networking and mobile edge computing. The new network architecture requires a data storage solution that is capable of functioning as the state store in the mobile network environment. Thus, we present an overview of promising data stores and evaluate their suitability. Further in this thesis we present the results of benchmarking the Apache Geode data store, as an example of a state management solution that could be leveraged in realising the coreless mobile network architecture. We discovered that the Apache Geode data store is, depending on configuration, capable of delivering the data model, consistency, high availability, scaling, throughput and latency that are required in our proposed architecture. ACM Computing Classification System (CCS): - Information systems ~ Distributed storage - Information systems ~ Hierarchical storage management - Networks ~ Middle boxes / network appliances - Networks ~ Mobile network

An Architecture for the Compilation of Persistent Polymorphic Reflective Higher-Order Languages

Persistent Application Systems are potentially very large and long-lived application systems which use information technology: computers, communications, networks, software and databases. They are vital to the organisations that depend on them and have to be adaptable to organisational and technological changes and evolvable without serious interruption of service. Persistent Programming Languages are a promising technology that facilitate the task of incrementally building and maintaining persistent application systems. This thesis identifies a number of technical challenges in making persistent programming languages scalable, with adequate performance and sufficient longevity and in amortising costs by providing general services. A new architecture to support the compilation of long-lived, large-scale applications is proposed. This architecture comprises an intermediate language to be used by front-ends, high-level and machine independent optimisers, low-level optimisers and code generators of target machine code. The intermediate target language, TPL, has been designed to allow compiler writers to utilise common technology for several different orthogonally persistent higher-order reflective languages. The goal is to reuse optimisation and code-generation or interpretation technology with a variety of front-ends. A subsidiary goal is to provide an experimental framework for those investigating optimisation and code generation. TPL has a simple, clean type system and will support orthogonally persistent, reflective, higher-order, polymorphic languages. TPL allows code generation and the abstraction over details of the underlying software and hardware layers. An experiment to build a prototype of the proposed architecture was designed, developed and evaluated. The experimental work includes a language processor and examples of its use are presented in this dissertation. The design space was covered by describing the implications of the goals of supporting the class of languages anticipated while ensuring long-term persistence of data and programs, and sufficient efficiency. For each of the goals, the design decisions were evaluated in face of the results

The Genetics of IBD: From Susceptibility to Drug Response and Patient Outcome

Inflammatory bowel disease (IBD) is a group of immune-mediated autoinflammatory disorders, primarily manifesting in the gastrointestinal tract. Affecting millions of people around the world, IBD has a severe impact on patients’ quality of life. Several pharmacologic treatments have been available since the 1950s. However, the majority of patients either do not respond to a given therapy or lose response to a previously effective treatment and thus require therapeutic escalation. In the first research chapter of my thesis, I describe the results of the Personalised Anti-TNF Therapy in Crohn’s disease study. Immunogenicity to anti-TNF therapy is a major cause of loss of response, hypersensitivity reactions, and discontinuation of treatment in patients. Currently, immunogenicity cannot be predicted prior to treatment. My analysis has identified a strong dominant association in the HLA region on chromosome 6 (HLA-DQA1*05, P=5.9e-13; HR=1.90; 95% CI, 1.60 to 2.25). Around 40% of individuals of European ancestry carry HLA-DQA1*05, and the data suggest that around 95% of these would develop immunogenicity within the first year of infliximab monotherapy treatment (a common anti-TNF treatment regime). In the second research chapter of my thesis, I describe a genome-wide association study of thiopurine-induced liver damage (TILI). Ultimately, the study was underpowered to detect any associations of moderate effect size and did not detect any associations of high effect size amongst the common genetic variants. Interestingly, I was not able to replicate the association in PTPN22, which was reported to be a risk factor for drug-induced liver damage by Cirulli et al. – suggesting that its effect might be heterogeneous depending on the therapy. Finally, the third research chapter describes the initial analysis of the IBD 15x dataset – a whole-genome sequencing association study of around 7,000 IBD patients paired with 12,000 matching controls. I provide an overview of the sample quality control procedures and describe some of the novel challenges that sequencing studies bring in comparison to standard GWAS (e.g., sample cross-contamination due to index mismatching). Finally, I also provide the results of the initial meta-analysis of the exome-sequencing dataset produced by the Broad Institute. The results demonstrate that rare coding genetic variants play a role in IBD pathogenesis.Wellcome Trus

An Institutional Design for Sustainable Foreign Forest Carbon Projects in Developing Countries

Under the international climate legal regime, many tree planting and forest management activities have been conducted in developing countries with the intention to generate carbon offsets (forest carbon projects). However, studies have shown that some foreign forest carbon projects lead to severely unsustainable results. The current international institutional framework cannot guarantee the long-term environmental and social benefits. This study set out to investigate how to design institutional reforms to promote sustainable results in foreign forest carbon projects in developing countries. The study provides one possible solution to this question that lies in the existing governing systems of multilateral funds. _Part I_ reviews the international institutional framework on forest carbon projects in developing countries using doctrinal and historical approaches. _Part II_ analyses the incentive schemes and the financial streams among major project actors from developed and developing countries. _Part III_ presents a case study of China, which examines the national institutional framework and practices based on interviews and project-site visits. Based on the analysis in the previous parts, Chapter 9 confirms that multilateral funds, which invest in foreign forest carbon projects in developing countries as financial intermediaries between the North and the South, have institutional and economic advantages in addressing the problems identified in the institutional framework and in the incentive schemes. Ten measures are discussed and tailored to address identified problems, based on evidence from practice, and embedded in a workable existing system