A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients

Background Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene. Methods Six independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants. Results Amid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%. Conclusions Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.FEDER funds-a way to build Europe PI19/00553 PI16/00563 PI16/01898 SAF2015-68016-RGeneralitat de Catalunya 2017SGR1282 2017SGR496CERCA Program: Government of CataloniaXunta de GaliciaInstituto de Salud Carlos III. AES PI19/00340Spanish Government SAF2016-80255-REuropean Commission EFA086/15Instituto de Salud Carlos III European Commissio

Blockchain-based Decentralized Distribution Management in E-Journals

The application of blockchain in the context of E-Journal distribution to journalists is aimed at making the management paper adequately distributed and not misused. The security system in the distribution or management paper process of an open journal system is currently considered to be very lacking because one can duplicate the journal in an open journal system easily. Furthermore, it can be transferred to anyone who is not responsible. The security system in the distribution of an open journal system and the management of the management paper process is currently considered to be very lacking because one can duplicate the journal in an open journal system easily. Furthermore, it can be transferred to anyone who is not responsible. With the implementation of this blockchain technology, there are 3 (three) benefits, namely (1) The distribution of E-Journal in the Open Journal System is more targeted, and there are no errors. (2) The reputation of the Open Journal System becomes better with a sense of trust. This research will be implemented in an E-Journal in an Open Journal System using blockchain technology. (3) The management paper processing in the open journal system runs according to the procedure so that in the management process the distribution of soft copies and hard copies of the journal is protected from hacker threats, and this blockchain is used to guarantee its security

A Cross-National Comparison of Consumers\u27 Attitudes Toward Direct Marketing and Purchase Intention

Existing research indicates that attitudes toward the three elements of direct marketing (the source, mode, and response channel) influence consumers\u27 intentions to purchase directly marketed products. While research investigating attitudes and consumers\u27 response has been conducted in the U.S., there has been no research to date which examines attitude structures and purchase intentions towards direct marketing in a multi-country setting, in spite of the standardized global efforts of direct marketeers. This study presents findings on attitude structures regarding direct marketing for three affluent open markets, the U.S., Singapore, and the Netherlands and empirically investigates the relationships between these consumers\u27 attitudes toward the three elements of direct marketing and purchase intentions

Practical Run-time Checking via Unobtrusive Property Caching

The use of annotations, referred to as assertions or contracts, to describe program properties for which run-time tests are to be generated, has become frequent in dynamic programing languages. However, the frameworks proposed to support such run-time testing generally incur high time and/or space overheads over standard program execution. We present an approach for reducing this overhead that is based on the use of memoization to cache intermediate results of check evaluation, avoiding repeated checking of previously verified properties. Compared to approaches that reduce checking frequency, our proposal has the advantage of being exhaustive (i.e., all tests are checked at all points) while still being much more efficient than standard run-time checking. Compared to the limited previous work on memoization, it performs the task without requiring modifications to data structure representation or checking code. While the approach is general and system-independent, we present it for concreteness in the context of the Ciao run-time checking framework, which allows us to provide an operational semantics with checks and caching. We also report on a prototype implementation and provide some experimental results that support that using a relatively small cache leads to significant decreases in run-time checking overhead.Comment: 30 pages, 1 table, 170 figures; added appendix with plots; To appear in Theory and Practice of Logic Programming (TPLP), Proceedings of ICLP 201

A prototype mobile money implementation in Nigeria

Researchers have shown that majority of the populace in the developing nations are rural dwellers that do not have access to basic financial services and are poor. This class of people are peasant farmers and petty traders who rely mostly on remittances from their wards and relations in major cities and abroad to meet their financial obligations at home. The methods of remittances are encumbered with challenges. Mobile money is a tool that allows individuals to make financial transactions using mobile cell phones. Nigeria is one of the fastest growing telecoms nations of the world and the adoption of mobile money will help a great deal to solve the problems associated with remittances. In this paper, we present a short messages services (SMS) and unstructured supplementary service data (USSD) implementation of mobile money implementation in Nigeria modelled using Django and Python as the programming language, MySQL as the data store and Apache hypertext transfer protocol (HTTP) as the Web server. The system made comparative analysis with M-PESA implementation in Kenya: the first mobile money implantation in Africa. Furthermore, the system was tested among a selected few of the populace to evaluate the usability of the design. Findings revealed that the prototype implementation is user-friendly and can be used by all without many problems except for the illiterate populace; hence, the need to have a combined bank and agent-based implementation. This approach will help with time to reduce the number of unbanked populace, which is currently at 80%

A neural network-based framework for financial model calibration

A data-driven approach called CaNN (Calibration Neural Network) is proposed to calibrate financial asset price models using an Artificial Neural Network (ANN). Determining optimal values of the model parameters is formulated as training hidden neurons within a machine learning framework, based on available financial option prices. The framework consists of two parts: a forward pass in which we train the weights of the ANN off-line, valuing options under many different asset model parameter settings; and a backward pass, in which we evaluate the trained ANN-solver on-line, aiming to find the weights of the neurons in the input layer. The rapid on-line learning of implied volatility by ANNs, in combination with the use of an adapted parallel global optimization method, tackles the computation bottleneck and provides a fast and reliable technique for calibrating model parameters while avoiding, as much as possible, getting stuck in local minima. Numerical experiments confirm that this machine-learning framework can be employed to calibrate parameters of high-dimensional stochastic volatility models efficiently and accurately.Comment: 34 pages, 9 figures, 11 table

ATM automation: guidance on human technology integration

© Civil Aviation Authority 2016Human interaction with technology and automation is a key area of interest to industry and safety regulators alike. In February 2014, a joint CAA/industry workshop considered perspectives on present and future implementation of advanced automated systems. The conclusion was that whilst no additional regulation was necessary, guidance material for industry and regulators was required. Development of this guidance document was completed in 2015 by a working group consisting of CAA, UK industry, academia and industry associations (see Appendix B). This enabled a collaborative approach to be taken, and for regulatory, industry, and workforce perspectives to be collectively considered and addressed. The processes used in developing this guidance included: review of the themes identified from the February 2014 CAA/industry workshop1; review of academic papers, textbooks on automation, incidents and accidents involving automation; identification of key safety issues associated with automated systems; analysis of current and emerging ATM regulatory requirements and guidance material; presentation of emerging findings for critical review at UK and European aviation safety conferences. In December 2015, a workshop of senior management from project partner organisations reviewed the findings and proposals. EASA were briefed on the project before its commencement, and Eurocontrol contributed through membership of the Working Group.Final Published versio