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This paper was developed as part of an effort by the National Institute for Occupational Safety and Health (NIOSH) to identify risk factors associated with bumps in the prevention of fatalities and accidents in highly stressed, bump-prone ground conditions. Changes of failure mechanism with increasing confinement, from extensional-to shear-dominated failure, are widely observed in the rupture of intact specimens at the laboratory scale and in rock masses. In the previous analysis conducted in 2018, both unconfined and triaxial compressive tests were conducted to investigate the strength characteristics of some specimens of a Utah coal, including the spalling limits, the ratio of apparent unconfined compressive strength (AUCS) to unconfined compressive strength (UCS), the damage characteristics, and the post-yield dilatancy. These mechanical characteristics were found to be strongly anisotropic as a function of the orientation of the cleats relative to the loading direction. However, the transition from extensional to shear failure at the given confinements was not clearly identified. In this study, a total of 20 specimens were additionally prepared from the same coal sample used in the previous study and then tested under both unconfined and triaxial compressive conditions. The different confining stresses are used as analogs for different width-to-height (W/H) ratios of pillar strength. Although the W/H ratios of the specimens were not directly considered during testing, the equivalent W/H ratios of a pillar as a function of the confining stresses were estimated using an existing empirical solution. According to this relationship, the W/H at which in-situ pillar behavior would be expected to transition from brittle to ductile is identified.

While faults are commonly simulated as a single planar or non-planar interface for a safety or stability analysis in underground mining excavation, the real 3D structure of a fault is often very complex, with different branches that reactivate at different times. Furthermore, these branches are zones of non-zero thickness where material continuously undergoes damage even during interseismic periods. In this study, the initiation and the initial evolution of a strike-slip fault was modeled using the FLAC3D software program. The initial and boundary conditions are simplified, and mimic the Riedel shear experiment and the constitutive model in the literature. The FLAC3D model successfully replicates and creates the 3D fault zone as a strike-slip type structure in the entire thickness of the model. The strike-slip fault structure and normal displacement result in the formation of valleys in the model. Three panels of a longwall excavation are virtually placed and excavated beneath a main valley. The characteristics of stored and dissipated energy associated with the panel excavations are examined and observed at different stages of shear strain in the fault to evaluate bump potential. Depending on the shear strain in the fault, the energy characteristics adjacent to the longwall panels present different degrees of bump potential, which is not possible to capture by conventional fault simulation using an interface. Keywords: 3D fault zone, Strike-slip fault, FLAC3D, Bump potential, Energy characteristics

The pathological hallmark of Parkinson’s disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, where the dopaminergic neurons form five clusters called nigrosomes 1–5 (N1–N5). N1 is the largest and considered to be the most affected by PD, followed by N2, N4, N3, and N5. Recently, an MRI study suggested a sequential progression of loss from N1 to N4. As the extent of cortical thinning widens as PD progresses, we aimed to define cortical thinning patterns according to the differential involvement of N1 and N4 in PD patients. Cortical thickness was analyzed in 83 PD patients (29 with N1 loss on at least one side of the brain, but no N4 loss; and 54 with N4 loss on at least one side) and 35 healthy subjects with age, sex, disease duration, and intracranial volume as covariates. On patient-wise analysis, for areas with more cortical thinning than the controls, PD patients with N4 loss had wider cortical thinning involving more dorsolateral prefrontal cortex and temporal areas than PD patients with only N1 loss, but cortical thinning did not significantly differ between these two patient groups. However, cortical thinning was more apparent in hemisphere-level analysis with statistically significant clusters being found more in hemispheres with N4 loss than hemispheres with N1 loss in PD patients compared to normal hemispheres of the controls. Cortical thinning occurred in a similar propagation pattern to that seen with PD progression, supporting past hypotheses on the sequential progression of nigrosome loss from N1 to N4.

Bumps and other types of dynamic failure have been a persistent, worldwide problem in the underground coal mining industry, spanning decades. For example, in just five states in the U.S. from 1983 to 2014, there were 388 reportable bumps. Despite significant advances in mine design tools and mining practices, these events continue to occur. Many conditions have been associated with bump potential, such as the presence of stiff units in the local geology. The effect of a stiff sandstone unit on the potential for coal bumps depends on the location of the stiff unit in the stratigraphic column, the relative stiffness and strength of other structural members, and stress concentrations caused by mining. This study describes the results of a robust design to consider the impact of different lithologic risk factors impacting dynamic failure risk. Because the inherent variability of stratigraphic characteristics in sedimentary formations, such as thickness, engineering material properties, and location, is significant and the number of influential parameters in determining a parametric study is large, it is impractical to consider every simulation case by varying each parameter individually. Therefore, to save time and honor the statistical distributions of the parameters, it is necessary to develop a robust design to collect sufficient sample data and develop a statistical analysis method to draw accurate conclusions from the collected data. In this study, orthogonal arrays, which were developed using the robust design, are used to define the combination of the (a) thickness of a stiff sandstone inserted on the top and bottom of a coal seam in a massive shale mine roof and floor, (b) location of the stiff sandstone inserted on the top and bottom of the coal seam, and (c) material properties of the stiff sandstone and contacts as interfaces using the 3-dimensional numerical model, FLAC3D. After completion of the numerical experiments, statistical and multivariate analysis are performed using the calculated results from the orthogonal arrays to analyze the effect of these variables. As a consequence, the impact of each of the parameters on the potential for bumps is quantitatively classified in terms of a normalized intensity of plastic dissipated energy. By multiple regression, the intensity of plastic dissipated energy and migration of the risk from the roof to the floor via the pillars is predicted based on the value of the variables. The results demonstrate and suggest a possible capability to predict the bump potential in a given rock mass adjacent to the underground excavations and pillars. Assessing the risk of bumps is important to preventing fatalities and injuries resulting from bumps. Keywords: Bumps, Robust design, FLAC3D, Plastic dissipated energy, Multiple regression

Background and Aims: Nivolumab was the first immune checkpoint inhibitor approved for hepatocellular carcinoma (HCC). External beam radiation therapy (EBRT) is locally effective and may enhance the effectiveness of immunotherapy. This study investigated the efficacy and safety of concurrent nivolumab and EBRT in HCC with macrovascular invasion. Methods: In this phase II multicenter trial, patients with HCC and macrovascular invasion were concurrently treated with intravenous nivolumab (3 mg/kg every 2 weeks) and EBRT, followed by maintenance nivolumab until progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) and safety, and secondary endpoints were overall survival, time-to-progression, objective response rate, and disease control rate. Results: Between January 2020 and June 2021, 50 patients (male 84%, median age 62.5) were enrolled; 47 (94.0%) and 13 (26.0%) with portal (Vp1/2, n = 21; Vp3, n = 23; Vp4, n = 3) and hepatic vein invasion, respectively. Patients received EBRT (median dose: 50 [IQR 43–50] Gy) after the first nivolumab dose. The median number of nivolumab doses was 8.5. Median PFS was 5.6 (90% CI 3.6–9.9) months. Median overall survival and time-to-progression were 15.2 (90% CI 10.8–19.6) and 5.6 (90% CI 3.6–9.9) months, respectively. The objective response rate and disease control rate were 36.0% and 74.0%, respectively. The median duration of response was 9.9 months. Of 35 patients with follow-up data, 23 received subsequent systemic treatment, including atezolizumab-bevacizumab, sorafenib, lenvatinib, and regorafenib. Treatment-related any grade adverse events (AEs) and grade 3/4 AEs occurred in 40 (80.0%) and 6 (12.0%) patients, respectively. Common treatment-related AEs included pruritus (38.0%) and rash (16.0%), with no treatment-related deaths. Conclusion: Concurrent nivolumab therapy and EBRT showed encouraging PFS with acceptable safety in patients with advanced HCC and macrovascular invasion. Impact and implications: Immune checkpoint inhibitors, the standard care for advanced hepatocellular carcinoma (HCC), show relatively poor therapeutic effects in patients with advanced HCC and macrovascular invasion. In this investigator-initiated phase II study, we, for the first time, show that concurrent external beam radiation therapy with nivolumab, an immune checkpoint inhibitor, led to encouraging progression-free survival in patients with HCC and macrovascular invasion. The concurrent treatment was tolerable without significant safety concerns. Further randomized studies investigating the combination of immunotherapy and external beam radiation therapy are required. ClinicalTrials.gov identifier: NCT04611165