EVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0-68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom Go Hun Seo, Taeho Kim, and In Hee Choi contributed equally to this work.

The PedsQL 3.0 ESRD module may be useful as an ESRD-specific instrument to evaluate HRQOL in children; however, a larger, longitudinal prospective study is warranted.

To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P[4.94E-20, odds ratio (OR) [1.90)

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Three-dimensional numerical simulations were conducted to study temperature distributions and fluid flows during formation of humped beads in high speed gas metal arc welding (GMAW). Based on simulation and experimental results, the physical mechanisms associated with humping phenomenon were investigated and two conditions responsible for hump formation were identified: the formation of thin liquid channel induced by surface tension pinching force and premature solidification of the melt in the thin channel that divides the weld pool into a front and rear portion. A strong backward fluid flow that produced an accumulation of melt at the rear of the weld pool increased the size of humps. Although surface tension was shown to be important in hump formation, Marangoni flow induced by negative surface tension gradients was not significant for hump formation. The simulation results clarified the fluid flow associated with two different hump shapes. Experimental welds without bead humping were made at a lower travel speed and were also simulated to illustrate the differences in heat and fluid flow from humped beads.