Checkpoint Inhibitors in Multiple Myeloma: Intriguing Potential and Unfulfilled Promises

Immune dysregulation and alteration of the bone marrow microenvironment allowing plasma cells to escape immune surveillance are well-known factors associated with the proliferation of clonal plasma cells and development of multiple myeloma (MM). Whilst immunotherapeutic approaches are now commonplace in a wide spectrum of malignancies, this aberration of myeloma development gives rise to the biological rationale for the use of immune checkpoint inhibitors (ICIs) in MM. However, the initial experience with these agents has been challenging with limited single agent efficacy, significant toxicity, and side effects. Herein, we review the biological and immunological aspects of MM and ICIs. We discuss the basic biology of immune checkpoint inhibitors, mechanisms of resistance, and drug failure patterns, review the published clinical trial data for ICIs in MM, and look towards the future of ICIs for MM treatment.

Finite element modelling of UHPC under pulsating load using X-ray computed tomography based fiber distributions

The benefits of including fibers in ultra-high performance concrete (UHPC) are attributed to their good bond with the matrix and, hence, an optimal utilization of their properties. At the same time, though, fiber reinforcement may contribute to anisotropy in the composite material and induce weak areas. The influence of the fibers’ orientation on the material properties is a matter of current scientific discourse and it is known to play a vital role in structural design. In the case studies presented herein, mechanical laboratory tests using pulsating load regimes on UHPC with a strength of more than 200 MPa were simulated by use of finite element models. The orientations of the fibers were measured for each test sample prior to failure using an X-ray computed tomography (CT) scanner, and these orientations are explicitly implemented into the model. The paper discusses the methodology of merging data retrieved by CT image processing and state-of-the-art FE simulation techniques Moreover, the CT scanning was carried out throughout the testing procedure, which further enables the comparison of the mechanical tests and the FE models in terms of damage propagation and failure patterns. The results indicate that the overall fiber configuration and behavior of the samples can be realistically modelled and validated by the proposed CT-FE coupling, which can enhance the structural analysis and design process of elements produced with steel fiber reinforced and UHPC materials.

Mechanical properties of high-performance concrete under triaxial compression

It is well known that the mechanical properties of a material are related to lateral confinement. In this paper, 60 cylindrical high-performance concrete (HPC) specimens with different concrete strength grades were cast and subjected to a conventional triaxial experiment to study the mechanical properties of the material. The experimental results indicated that the specimens exhibited longitudinal splitting failure patterns under uniaxial compression and inclined plane shear failure patterns under triaxial compression. The stress–strain curves were divided into three stages: an elastic rising stage, a plastic rising stage and a softening descending stage. The application of lateral confining pressure effectively increased the triaxial compressive strength. As the concrete strength increased, the descending stage of the stress–strain curves became steeper, indicating an increase in brittleness. Based on the experimental results, the failure criterion of the HPC was analysed using the Drucker–Prager yield criterion and Kotsovos failure theory. The parameters of the Drucker–Prager yield criterion were determined, and the applicable range of the Kotsovos failure theory was also obtained.

The Neutrosophic Lognormal Model in Lifetime Data Analysis: Properties and Applications

The lognormal distribution is more extensively used in the domain of reliability analysis for modeling the life-failure patterns of numerous devices. In this paper, a generic form of the lognormal distribution is presented that can be applied to model many engineering problems involving indeterminacies in reliability studies. The suggested distribution is especially effective for modeling data that are roughly symmetric or skewed to the right. In this paper, the key mathematical properties of the proposed neutrosophic lognormal distribution (NLD) have been derived. Throughout the study, detailed examples from life-test data are used to confirm the mathematical development of the proposed neutrosophic model. The core ideas of the reliability terms, including the neutrosophic mean time failure, neutrosophic hazard rate, neutrosophic cumulative failure rate, and neutrosophic reliability function, are addressed with examples. In addition, the estimation of two typical parameters of the NLD by mean of maximum likelihood (ML) approach under the neutrosophic environment is described. A simulation experiment is run to determine the performance of the estimated parameters. Simulated findings suggest that ML estimators effectively estimate the unknown parameters with a large sample size. Finally, a real dataset on ball bearings failure times has been considered an application of the proposed model.

RT-4 Treatment outcome of proton beam therapy for glioblastoma

Introduction: Proton beam therapy enables high dose irradiation for tumors while reducing the dose to surrounding normal tissue due to the sharp energy peak called the Bragg peak. We retrospectively analyzed the efficacy of the high dose radiotherapeutic strategy using proton beam for glioblastoma (GBM) in our institution. Methods: Twenty-nine patients with newly diagnosed GBM who underwent high dose proton beam therapy concomitant with temozolomide were investigated. All patients received hyperfractionated concomitant radiotherapy consisting of X-ray radiotherapy (50.4Gy in 28 fractions) and proton beam therapy (46.2Gy [RBE] in 28 fractions). The survival outcome and adverse events were analyzed. Results: The median overall survival time and progression free survival time for all 29 patients were 31.0 months (95%CI, 25.9–36.1) and 11.0 months (95%CI, 7.8–14.2), respectively. No significant survival difference according to the MGMT methylation status was shown. Failure patterns after proton beam therapy included 17 cases of local recurrence, 3 cases of distant recurrence, and 5 cases of dissemination. Although there was no significant difference in time to recurrence according to the failure pattern, there was a tendency of longer survival in the local recurrence group. Regarding adverse events, radiation necrosis was observed in 8 cases (including 2 asymptomatic cases). The median time to onset of necrosis after radiation was 18.2 months (95%CI, 10.3–26.2). There were 5 cases of long survivor over 5 years out of 29 cases (17.2%). Of these, 4 cases developed radiation necrosis. Conclusions: Our results indicate that high dose proton beam therapy of 96.6Gy (RBE) prolonged survival in selected GBM patients. Particularly in long survivors, special attention and effective treatment to radiation necrosis is a remaining problem.

Destruction of coal seams during mining by dredging machines

The monograph is devoted to the issues of scientific substantiation of ways to improve the efficiency of the functioning of the executive bodies of coal mining machines used in the underground mining of coal seams, which are of great practical importance. The results of studies on the reliability of destructive organs are new in the formulation and not previously published in the monograph format. A model is described and a physical interpretation of the failure patterns of auger assemblies and elements is given, methods for assessing the reliability and efficiency of using augers and cutting tools for specific operating conditions using traditional probabilistic and new energy approaches are proposed. It is addressed to engineering and technical workers of design institutions, factories and mines engaged in the design and operation of cleaning combines and plows.

Stress Distribution and Mechanical Behaviour of Rock Mass Containing Two Openings Underground: Analytical and Numerical Studies

In this study, stress solution for rock mass containing two rectangular openings was calculated based on the Schwarz alternating method to investigate the stress distribution in rock mass around openings with different layouts. In addition, large-scale numerical models were further established for the two-opening system by means of the PFC-FLAC coupling method, in which the stress evolution, failure patterns, and acoustic emission (AE) events were presented. With the combination of analytical and numerical solutions, the interaction mechanism between two openings under different layouts was discussed from the perspective of stress and failure. The result shows that the confining stress within a certain range contributes to relieving tensile stress concentration around openings. The stress condition within the connecting area and coalescence pattern between two adjacent openings is dominated by their layout. Compared with small-size rock specimens in laboratory tests, the failure patterns around openings show a better agreement with the stress concentration characteristics determined by analytical stress solutions.

Effect of Layer Thickness on the Physical and Mechanical Properties of Sand Powder 3D Printing Specimens

The application of sand powder three-dimensional (3D) printing technology in the field of rock mechanics and mining engineering has tremendous potential, but it is still in the preliminary exploration stage. This study investigated the effect of printing layer thickness on the physical and mechanical properties of rock-like specimens with sand powder 3D printing. Quartz sand powder was used as the printing material, and the specimens were prepared with three different layer thicknesses of 0.2, 0.3, and 0.4 mm. Uniaxial compression tests with a combination of digital image correlation (DIC), acoustic emission (AE) and 3D microscope observations were performed to analyze the mechanical properties and failure patterns of the specimens during loading. Experimental findings showed that increasing the layer thickness from 0.2 to 0.4 mm would result in a decrease in the weight, density, uniaxial compression strength, and elastic modulus of the specimens. The stress-strain curve, deformation and failure patterns, crack growth process, and AE characteristics of the specimens with a layer thickness of 0.2 mm are similar to the AE characteristics of rock-like material, whereas the specimens with layer thicknesses of 0.3 and 0.4 mm deform like a ductile material, which is not appropriate for simulation of coal or rock mass. In future studies, rock-like specimens should be prepared with a small layer thickness.