Instability of dykes at Seven Sisters Generating Station

Water-retention dykes at Seven Sisters Generating Station in Manitoba have experienced irregular instabilities since they were heightened in the late 1940s. An investigation was undertaken to compare three locations at the site, one section of dyke that had experienced previous instability, a second section that had remained stable, and a third, background location that had not experienced dyke loading. The investigation included laboratory tests, field tests, and computer modelling. The laboratory tests indicated anisotropic stiffness and brittle strain-softening behaviour in the highly plastic clay beneath the dykes. Results from the stable and unstable sections showed greater brittleness and anisotropy at the unstable section. Pore fluid chemistry tests for cation and anion concentrations showed considerable reductions in concentrations of calcium and sulphate beneath the dykes compared with those of the background section. This suggested leaching of gypsum in the foundation soil. Computer modelling was done using seepage, stress-deformation, and slope stability software. Results indicated that the stable and unstable sections both had safety factors greater than unity if "post-peak" strengths were used. Both were close to unity if residual strengths were used. The results suggest that time- and location-dependent depletion of gypsum cementation bonds caused by seepage beneath the dykes has increased the brittleness and anisotropy and reduced stability with time

Tumor molecular profiling in advanced pediatric brain tumors.

e21516 Background: With the advent of high-throughput molecular profiling, clinical outcome in pediatric cancers has greatly improved due to our greater understanding of genetic origin of pediatric cancer, and availability of biomarker specific treatment options. However, pediatric brain tumors continue to be challenging in terms of therapy. The goal of this study was to evaluate the utility of integrative clinical sequencing in pediatric patients with brain tumors. Methods: Targeted exome sequencing of 562 genes in paired tumor-normal DNA was performed on 14 patients and tumor DNA and RNA was sequenced on additional 4 patients. Sequence analysis identified SNVs, indels, copy number events, fusions, alternate transcripts, breakpoints, TMB and MSI status. Clinically, actionable alterations were identified which could be targeted by FDA approved agents or clinical trials. Results: A total of 18 patients (1-17 y.o.) with low grade (n = 5) and high grade (n = 13) brain tumors were profiled. The cohort consisted of a spectrum of GBMs (45%), medulloblastomas (10%) astrocytomas (22%), and other brain tumors (23%). At least one targetable, driver alteration was identified in 83% of all patients, and 92% of high-grade patients had at least one targetable driver event. Targetable mutations were identified in histone and chromatin modifier genes like H3F3A in 3/18 cases (17%), SETD2, ARID1A, PBRM1 in 2/18 cases (11%), activation of PI3K/AKT/mTOR pathway genes in 6/18 cases (33%), DNA repair genes NBN, ATRX and BRCA2 in 3/18 cases (17%); BRAF V600E in 3 high-grade and a KIAA1549/BRAF fusion in a low-grade tumor, activation of cell cycle in 2/18 cases (11%), activation of FGFR pathway with FGFR1/TACC1 fusion and activating mutation in 2/18 cases (11%), activation of PDGFRA in 2/18 samples (11%), TP53 mutations in 4/18 cases (22%). A breakpoint translocation concurrent with LOH of PTCH1 locus was noted in a medulloblastoma patient. High TMB or MSI instability was not observed. Conclusions: Our results underline the importance of clinical sequencing in identifying targetable markers in high- risk brain tumors. Although limited by small sample size, our study highlights the need for ongoing clinical trials to integrate the genomic discoveries leading to better clinical outcomes. </jats:p