Diagnostic yield of genetic testing in a multinational heterogeneous cohort of 2088 DCM patients

BackgroundFamilial dilated cardiomyopathy (DCM) causes heart failure and may lead to heart transplantation. DCM is typically a monogenic disorder with autosomal dominant inheritance. Currently disease-causing variants have been reported in over 60 genes that encode proteins in sarcomeres, nuclear lamina, desmosomes, cytoskeleton, and mitochondria. Over half of the patients undergoing comprehensive genetic testing are left without a molecular diagnosis even when patient selection follows strict DCM criteria.Methods and resultsThis study was a retrospective review of patients referred for genetic testing at Blueprint Genetics due to suspected inherited DCM. Next generation sequencing panels included 23–316 genes associated with cardiomyopathies and other monogenic cardiac diseases. Variants were considered diagnostic if classified as pathogenic (P) or likely pathogenic (LP). Of the 2,088 patients 514 (24.6%) obtained a molecular diagnosis; 534 LP/P variants were observed across 45 genes, 2.7% (14/514) had two diagnostic variants in dominant genes. Nine copy number variants were identified: two multigene and seven intragenic. Diagnostic variants were observed most often in TTN (45.3%), DSP (6.7%), LMNA (6.7%), and MYH7 (5.2%). Clinical characteristics independently associated with molecular diagnosis were: a lower age at diagnosis, family history of DCM, paroxysmal atrial fibrillation, absence of left bundle branch block, and the presence of an implantable cardioverter-defibrillator.ConclusionsPanel testing provides good diagnostic yield in patients with clinically suspected DCM. Causative variants were identified in 45 genes. In minority, two diagnostic variants were observed in dominant genes. Our results support the use of genetic panels in clinical settings in DCM patients with suspected genetic etiology

Projektioppiminen automaatiosuunnittelussa

Hajautettujen automaatiojärjestelmien olemus on muuttunut viimeisten vuosikymmenten aikana uusien älykkäiden kenttälaitteiden ja väyläratkaisujen tuodessa niihin entistä enemmän hajautusta. Laajeneva teknologinen paletti ja sen omaksuminen tutkintoon johtavissa opinnoissa vaatii käytännön projekteja. Tässä artikkelissa kerrotaan TUNI-korkeakouluyhteisön Tampereen ammattikorkeakoulun (TAMK) ja Tampereen yliopiston (TAU) automaatiokoulutusten laboratoriotilojen yhteiskäytöstä yhden harjoituscasen kehityskaaren kautta

Computer-supported collaborative learning : Praxes in new cell-oriented configurable PC-classroom

Currently, technology-enhanced learning environments are a research hotspot in engineering education. Universities invest in modern environments equipped with the newest audiovisual hardware, computers and web-technologies. These environments support learner-centred model of education, which highlights active role of learners, learning-by-doing, and collaborative learner autonomy in a democratic atmosphere. Therefore, traditional teacher-led classrooms can be transformed to more diverse and more creative environments in which teachers and learners have relatively different roles compared with the traditional classroom. In this paper, we present layout, construction and hardware of our newly developed technology-mediated, configurable, and cell-oriented PC-classroom, which play a key role in our teaching development. We exemplify how the classroom has helped us to improve our automation science and control engineering education. To be more specific, we have adopted the well-known concept of computer-supported collaborative learning (CSCL), which concerns how students can learn together with the help of computers. We also demonstrate how redefining and redesigning the nature of activities occurring in modern learning environments can improve the effectiveness of contact teaching, and hence, allow learning episodes to be more impactful compared with the traditional teacher-led classroom. We would like to pinpoint that redefinition and redesign have allowed us, as teachers, to take the position of a facilitating guide, or mentor, which work in close cooperation with students, and thereby, is able to strengthen the knowledge level of students through intellectual face-to-face discussion as well as through technology-supported communication. Furthermore, our new classroom has enabled hands-on, competitive, cyber-physical attack-defence events to be conducted, which improve our automation security training. The events have invited participants from industry and academia, but most importantly, they have involved students. During the events, we have offered opportunities for students to make demonstration-of-skills to the participants from business. As a consequence, the new environment has enabled acts of openings for university-business cooperation in terms of education and recruit, free of charge. To our experience and according to student feedback, our redefined ways of conducting teaching has improved student motivation as well as increased their timely investment towards learning activities, which has eventually translated to better grades and overall satisfaction.publishedVersionPeer reviewe

Analyzing Reliability of the Communication for Secure and Highly Available GOOSE-Based Logic Selectivity

In an electrical distribution network, Logic Selectivity significantly reduces both the number and duration of outages. Generic Object-Oriented Substation Events (GOOSE) have a key role in the decision-making process of substation protection devices using GOOSE-based Logic Selectivity. GOOSE messages are exchanged between remote protection devices over the communication network. Secured communication with low latency and high reliability is therefore required in order to ensure reliable operation as well as meeting real-time requirement of the Logic Selectivity application. There is thus a need to evaluate feasibility of the selected communication network technology for Logic Selectivity use cases. This paper analyzes reliability of cellular 4G/LTE Internet for GOOSE communication in a Logic Selectivity application. For this purpose, experimental lab set-ups are introduced for different configurations: ordinary GOOSE communication, secured GOOSE communication by IPsec in Transport mode, and redundant GOOSE communication using the IEC 62439-3 Parallel Redundancy Protocol. In each configuration, the GOOSE retransmissions are recorded for a period of three days and the average GOOSE transmission time is measured. Furthermore, the measured data is classified into histograms and a probability value for communication reliability, based on the transmission time, is calculated. The statistical analysis shows that 4G Internet satisfies the real-time and reliability requirements for secure and highly available GOOSE-based Logic Selectivity

Using IEC CIM standards and SOA Technology for Coordinated Voltage Control Application

Distribution System Operators (DSOs) rely on an increasing number of software applications for network operation and management. These applications need to exchange data with each other smoothly and efficiently. To facilitate inter-application communications and improve interoperability, IEC Common Information Model (CIM) standards and enterprise integration technologies, such as Service-oriented architecture (SOA), can be used. This paper focuses on one distribution management use case – “Coordinated Voltage Control”, explains how CIM standards and SOA technologies can utilized to integrate Coordinated Voltage Control Matlab software with external systems such as SCADA. The paper covers design, implementation and laboratory demonstration for the communication aspect of this use case.acceptedVersionPeer reviewe