A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Development of energy dissipating cladding connections for passive control of building seismic response

Ph.D.Barry J. Goodn

A comparison study of Catastrophe Modeling vs. Performance-Based Design

The paper presents the methodologies at the core of catastrophe modeling (CM) and performance-based design (PBD). Both CM and PBD are probabilisitic methods, in which the probability of achieving a certain hazard intensity is calculated and coupled with an estimate of the vulnerability or fragility of a certain building exposure to get an estimate of the exposure behavior, as well as of the expected damage and losses. Probabilistic CM is a well established field applied to all sorts of hazards, including the treatment of multi-hazards, whereas application of PBD to hazards other than seismic is a more recent development in structural engineering. CM is more oriented towards computing financial losses for the insurance industry and solving emergency management or community recovery issues, while PBD is oriented at guiding a particular building owner/designer in making the right design or retrofitting decisions. This paper explores similarities and differences between CM and PBD, especially regarding how the vulnerabilities or fragilities are derived in each case, how the uncertainties are treated, and how the two methodologies could benefit from each other

Probabilistic treatment of storm rotation and wind-driven rain deposition in a hurricane model

Hurricane catastrophe vulnerability models aim to capture the average building exterior and interior damages under extreme uncertainty. Interior damages, which may represent the majority of the repair bill are primarily due to wind driven rain intrusion. Rain intrusion is highly dependent on the storm direction with respect to the building. This paper presents a methodology to capture the effects of storm rotation on the wind driven rain that an “average” building would be exposed to during a hurricane. Two statistical methods are investigated and compared to best capture these effects with the goal of combining a time dependent rain model with a non-time dependent physical damage model.Non UBCUnreviewedThis collection contains the proceedings of ICASP12, the 12th International Conference on Applications of Statistics and Probability in Civil Engineering held in Vancouver, Canada on July 12-15, 2015. Abstracts were peer-reviewed and authors of accepted abstracts were invited to submit full papers. Also full papers were peer reviewed. The editor for this collection is Professor Terje Haukaas, Department of Civil Engineering, UBC Vancouver.FacultyResearche

Experimental and Computational Performance Analysis of a Multi-Sensor Wireless Network System for Hurricane Monitoring

A wireless sensor network system was developed at Florida Institute of Technology to monitor wind induced pressure on low-rise residential building roofs during hurricane events. The system was tested to evaluate the performance of the sensors and their reliability to measure accurate pressure variations. The reliability of the pressure sensors is established by comparing measurements with secondary references and basic Bernoulli theory. The effects of sensor case, wind gusts, wind direction and structural vibration on the measured pressure are also presented. The system was tested in a wind tunnel, on top of a van on a highway road test, and at the University of Florida hurricane simulator. These tests revealed that the pressure readings were sensitive to mechanical vibrations and the sensor case shape, only when facing the windward direction. Some computational fluid dynamics analysis was also employed to verify the sensors performance and to develop reliable computational tools to simulate hurricane effects

LEFT-VENTRICULAR CONTRACILITY AFTER HYPOTHERMIC PRESERVATION - PREDICTIVE VALUE OF P-31 - NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

International audienceAbstract: Early graft failure accounts for a substantial portion of the mortality after heart transplantation. This factor underscores the need for the development of reliable methods for predicting graft performance and thus ensuring optimal clinical outcome. The aim of this study was to describe the link between myocardial metabolism evaluated throughout preservation with the use of phosphorus 31-nuclear magnetic resonance spectroscopy and ventricular contractility after reperfusion. Thirteen pig hearts were excised and preserved from 3 to 12 hours with clinical techniques. During preservation the hearts underwent, phosphorus 31-nuclear magnetic resonance spectroscopy. After reperfusion, left ventricular contractility was evaluated with an isolated heart model undergoing isovolumetric contraction. Throughout storage, beta-adenosine triphosphate remained stable and intracellular pH and phosphocreatine decreased exponentially, whereas inorganic phosphate increased exponentially. Intracellular pH, phosphocreatine, inorganic phosphates measured at the onset of preservation, and intracellular pH and phosphocreatine measured at the end of preservation correlated significantly with the left ventricular contractility after reperfusion. We conclude that the metabolic state of myocardium at excision is especially important and that phosphorus 31-nuclear magnetic resonance evaluation of the heart during preservation appears to provide reliable indexes for predicting subsequent ventricular contractility after reperfusion