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After a long period of geological tectonic action, the rock mass develops defects such as pores and fissures of different sizes and scales. The mechanical properties of the rock are largely affected by these discontinuous structures, and there will be obvious stress concentration at the edge of the hole inside the rock. Under the action of concentrated stress, cracks initiate, expand, and penetrate from the edge of the hole to form the final fracture surface and cause instability and failure of the rock mass. In practical engineering, due to the limitation of various factors, it is impossible to conduct uniaxial compressive strength test for each geotechnical engineering. Therefore, the rock in the weak part of the project can be selected as the test specimen before the indoor physical tests. In this paper, the static uniaxial compression test of specimens with circular holes with different diameters is carried out. Digital Image Correlation (DIC) monitoring system is used to observe the test process in real time; then, the data from uniaxial compression test and DIC monitoring test are obtained. At the same time, the macroscopic failure characteristics and crack propagation law of rock specimens are obtained, and the evolution law of strain field during the failure process of rock specimens is also obtained. Meanwhile, Realistic Failure Process Analysis (RFPA) is carried out to verify the accuracy of static uniaxial compression physical tests numerically. Physical tests show that the uniaxial compressive strength of marble specimens with circular holes and the dispersion of measured peak stress data decrease with the increase of hole diameter. The main failure type of marble specimens with circular holes is tension shear failure; the macroscopic failure zone of the sample, the strain field localization zone, and the maximum shear stress field of the numerical test are distributed in a semi-“X” shape with the hole as the center. The localization zone of the strain field on the specimen is usually the region of crack initiation, propagation, and penetration on the surface of the marble specimens. It also shows that specimen breaks in the radial direction along the y-axis of the circular hole, and cracks connecting both ends of the circular hole and the specimen are generated on the specimen. It is of great theoretical value and practical significance to the influence of the cavities in the rock specimens on the stress and strain characteristics and the initiation, propagation, and penetration modes.

Background and Aims: Guillain-Barré syndrome (GBS) is an acute, self-limited, immune-mediated peripheral neuropathy. Current treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange, which may not sufficiently benefit severely affected patients. This study evaluated the efficacy and safety of eculizumab add-on therapy to IVIg (standard-of-care treatment) in patients with severe GBS., Methods: This phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial (NCT04752566), enrolled Japanese adults (age ≥ 18 years) with severe GBS (Hughes functional grade [FG] score FG3 or FG4/FG5 within 2 weeks of onset of GBS). Participants were randomized 2:1 to receive intravenous infusion of eculizumab or placebo (once weekly for 4 weeks) with IVIg treatment with 20 weeks of follow-up. Primary efficacy endpoint was the time to first reach FG score ≤1 (able to run). Key secondary endpoints were proportion of participants achieving FG ≤1 at weeks 8 and 24 and FG improvement ≥3 at week 24. Pharmacodynamic analysis of serum free C5 concentration over time was performed. Safety was evaluated., Results: The analysis included 57 participants (eculizumab, n = 37; placebo, n = 20). Primary endpoint was not achieved (hazard ratio, 0.9; 95% CI, 0.45-1.97; p = .89). Key secondary endpoints did not reach statistical significance. Serum C5 concentration was reduced by 99.99% at 1 h postdose and sustained to week 5 but returned to baseline at the end of follow-up period. No new safety signals for eculizumab were identified., Interpretation: Although well tolerated, eculizumab treatment did not show significant effects on motor function recovery compared to placebo in patients with GBS., (© 2024 Peripheral Nerve Society.)

This open-label, single-period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130-mg evacetrapib oral dose and 4-h intravenous (IV) infusion of 175 µg [(13) C8 ]-evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [(13) C8 ]-evacetrapib using high-performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration-time curve (AUC) from zero to infinity (AUC[0-∞]) and to the last measureable concentration (AUC[0-tlast ]), were calculated. Bioavailability was calculated as the ratio of least-squares geometric mean of dose-normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2-47.6%) for AUC(0-∞) and 44.3% (90% CI: 41.8-46.9%) for AUC(0-tlast ). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a (13) C-labeled IV microdose tracer at about 1/1000(th) the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability., (© 2015 The Authors Journal of Labelled Compounds and Radiopharmaceuticals Published by John Wiley & Sons Ltd.)