BACKGROUND: Epi proColon® is a new blood-based colorectal cancer (CRC) screening test designed to determine the methylation status of a promoter region of the SEPT9 (septin 9) gene in cell-free DNA isolated from plasma. We describe the analytical and clinical performance of the test.
A comparative study of OH, O3, and H2O equilibrium aqueous solvation and gas-phase accommodation on liquid water at 300 K is performed using a combination of ab initio calculations and molecular dynamics simulations. Polarizable force fields are developed for the interaction potential of OH and O3 with water. The free energy profiles for transfer of OH and O3 from the gas phase to the bulk liquid exhibit a pronounced minimum at the surface, but no barrier to solvation in the bulk liquid. The calculated surface excess of each oxidant is comparable to calculated and experimental values for short chain, aliphatic alcohols. Driving forces for the surface activity are discussed in terms of the radial distribution functions and dipole orientation distributions for each molecule in the bulk liquid and at the surface. Simulations of OH, O3, and H2O impinging on liquid water with a thermal impact velocity are used to calculate thermal accommodation (S) and mass accommodation (alpha) coefficients. The values of S for OH, O3, and H2O are 0.95, 0.90, and 0.99, respectively. The approaching molecules are accelerated toward the liquid surface when they are approximately 5 angstroms above it. The molecules that reach thermal equilibrium with the surface do so within 2 ps of striking the surface, while those that do not scatter into the gas phase with excess translational kinetic energy in the direction perpendicular to the surface. The time constants for absorption and desorption range from approximately 35 to 140 ps, and the values of alpha for OH, O3, and H2O are 0.83, 0.047, and 0.99, respectively. The results are consistent with previous formulations of gas-phase accommodation from simulations, in which the process occurs by rapid thermal and structural equilibration followed by diffusion on the free energy profile. The implications of these results with respect to atmospheric chemistry are discussed.
We recently described a disorder termed Huntington disease-like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W). We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.
BackgroundScreening improves outcomes related to colorectal cancer (CRC); however, suboptimal participation for available screening tests limits the full benefits of screening. Non-invasive screening using a blood based assay may potentially help reach the unscreened population.ObjectiveTo compare the performance of a new Septin9 DNA methylation based blood test with a fecal immunochemical test (FIT) for CRC screening.Design: In this trial, fecal and blood samples were obtained from enrolled patients. To compare test sensitivity for CRC, patients with screening identified colorectal cancer (n = 102) were enrolled and provided samples prior to surgery. To compare test specificity patients were enrolled prospectively (n = 199) and provided samples prior to bowel preparation for screening colonoscopy.MeasurementsPlasma and fecal samples were analyzed using the Epi proColon and OC Fit-Check tests respectively.ResultsFor all samples, sensitivity for CRC detection was 73.3% (95% CI 63.9–80.9%) and 68.0% (95% CI 58.2–76.5%) for Septin9 and FIT, respectively. Specificity of the Epi proColon test was 81.5% (95% CI 75.5–86.3%) compared with 97.4% (95% CI 94.1–98.9%) for FIT. For paired samples, the sensitivity of the Epi proColon test (72.2% –95% CI 62.5–80.1%) was shown to be statistically non-inferior to FIT (68.0%–95% CI 58.2–76.5%). When test results for Epi proColon and FIT were combined, CRC detection was 88.7% at a specificity of 78.8%.ConclusionsAt a sensitivity of 72%, the Epi proColon test is non- inferior to FIT for CRC detection, although at a lower specificity. With negative predictive values of 99.8%, both methods are identical in confirming the absence of CRC.Trial RegistrationClinicalTrials.gov NCT01580540
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