<p>Supplementary Figure S1 shows a summary of the cohorts of xenografts used in each experiment.</p>
\n \n\n \n \n<p>Supplementary Figure S3 shows the MRI analysis steps.</p>
\n \n\n \n \nQUESTION: New spinal implants need to be tested for primary stability in vitro under standardized laboratory conditions. To ensure the reliability of the test procedures, quality assurance standards in accordance with ISO 9000 were introduced to standardize testing including experimental set ups, loading and test frequency. These standards, however, require a relatively long time to implement. METHOD: The LSP test was used to compare various surface treatments by different shot peening processes applied to spinal rods for dorsal spine implant systems. 6 rods made of two different cp-Titanium materials (Ti-2 and Ti-4) were tested. Dynamic tests were performed with the MTS 810 mono-axial servo-hydraulic test equipment. Beginning with a load of 200 N the rods were subjected to tensile and compressive loads, which were increased in steps of 100 N after every 50.000 cycles until rod failure. RESULTS: Results were available after one to two weeks. The best results (LSP 167 million) were achieved with Ti-4 rods shot peened with steel balls and glass beads. In comparison, the lowest LSP value of 81 million was found with Ti-2 rods shot peened with glass beads only. CONCLUSION: This high speed testing method has reduced the development time from two years to 6 months.
\n \n\n \n \n<p>Supplementary Table 8. Differential gene expression results (post-DESeq2 analysis) for BRAF, KRAS, NRAS, and the EGFR-ligands AREG and EREG across two normal-colorectum RNAseq cohorts. Sorted by adjusted p.values (Benjamini-Hochberg).</p>
\n \n\n \n \n<p>Supplementary Table 1. Details of each cohort included in the study</p>
\n \n\n \n \n<p>Supplementary Figure 2. Scaled Schoenfeld residuals for corresponding fixed-effect models, inclusive of study as a categorical variable, relating to mixed-effects survival models in Table 2. A. Model I compares BRAF classes across all patients irrespective of additional Ras mutation; B. Model II compares Class 1 without Ras vs Class 3 with Ras mutations; C. Model III examines additional Ras mutation status within Class 3. P-values represent significance of violation of proportional hazards assumptions.</p>
\n \n\n \n \n<p>Supplementary Table 2. PCR Primer sequences for validation of FFPE samples</p>
\n \n\n \n \n<p>Supplementary Figure 4. Kaplan-Meier survival curves of unadjusted overall survival (OS, months) for CRCs harboring a Class 1, 2, or 3 BRAF mutation. A: Overall survival by BRAF class irrespective of additional Ras status. B: Class 1, 2, and 3 in the absence of additional Ras. C: Class 1 and 3 absent additional Ras, and class 3 with additional Ras. Survival as shown is not corrected for covariates, whereas mixed-effects models including several covariates are reported in the main text and Table 2. Class 2 samples with survival data containing additional Ras status were insufficient for this analysis, as discussed in the main text.</p>
\n \n\n \n \n<p>Supplementary Table 5. 100,000 Genomes Project: Clonality estimates for atypical variants harbouring additional Ras pathway mutation with sufficient data available.</p>
\n \n\n \n \n<p>Supplementary Tables 9a-c. Gene-set enrichment analaysis (GSEA) results comparing classes of BRAF-mutant CRCs with and without additional Ras mutation.</p>
\n \n\n \n \n<p>Supplementary Table 7. Logistic regression models of CMS groups by BRAF mutation class, with covariates: tumour location (left or right colon), MSI status, age, sex, and additional Ras status (Class 1/2/3 left, A-B-C right).</p>
\n \n\n \n \n<p>Supplementary Figure 1. Study and data availability overview (see Supplementary Table 1).</p>
\n \n\n \n \n<p>Supplementary Data 1. Sanger sequencing chromatograms presented in Figure 3C-D.</p>
\n \n\n \n \n<p>Supplementary Text 1. Comparison between the A-B-C and 1-2-3 BRAF classification systems.</p>
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