Fatigue analysis of restored teeth longitudinally cracked under cyclic loading

ObjectiveTo investigate the fatigue behavior of restored teeth, in particular the mechanisms of longitudinal dentinal cracking under cyclic mechanical loading, using finite element analysis (FEA) and the stress-life (S-N) approach.MethodsTen root-filled premolars restored with resin composites were subjected to step-stress cyclic loading to produce longitudinal cracks. Fracture loads and number of cycles completed at each load level were recorded. FEA was used to predict the stress amplitude of each component under the global cyclic load. Both intact and debonded conditions were considered for the dentin-composite interface in the FEA. The predicted stress concentrations were compared with the fracture patterns to help elucidate the failure mechanisms. The S-N approach was further used to predict the lifetimes of the different components in the restored teeth. Cumulative fatigue damage was represented by the sum of the fractions of life spent under the different stress amplitudes.ResultsLongitudinal cracks were seen in ~50% of the samples with a mean fracture load of 770 ± 45 N and a mean number of cycles to failure of 32,297 ± 12,624. The longitudinal dentinal cracks seemed to start near the line angle of the cavity, and propagated longitudinally towards the root. The sum of fractions of life spent for the dentin-composite interface exceeded 1 after ~7000 cycles when that for dentin was much lower than 1, indicating that interfacial debonding would occur prior to dentin fracture. This was supported by micro-CT images showing widened interfacial space in the cracked samples. In the debonded tooth, FEA showed dentinal stress concentrations at the gingival wall of the cavity, which coincided with the longitudinal cracks found in the cyclic loading test. The sum of fractions of life spent for dentin was close to 1 at ~30,000 cycles, similar to the experimental value.SignificanceDebonding of the dentin-composite interface may occur prior to longitudinal cracking of dentin in root-filled teeth under cyclic loading. The approximate time of occurrence for these events could be estimated using fatigue analysis with stresses provided by FEA. This methodology can therefore be used to evaluate the longevity of restoration designs for root-filled teeth.     

How effective has the Spanish lockdown been to battle COVID-19? A spatial analysis of the coronavirus propagation across provinces

This paper examines the propagation of COVID-19 across the Spanish provinces and assesses the effectiveness of the Spanish lockdown of the population implemented on March 14, 2020 in order to battle this pandemic. To achieve these objectives, a standard spatial econometric model used in economics is adapted to resemble the popular reproduction models employed in the epidemiological literature. In addition, we introduce a counterfactual exercise that allows us to examine the Gross domestic product (GDP) gains of bringing forward the date of the Spanish Lockdown. We find that the number of COVID-19 cases would have been reduced by 70.4% in the absence of spatial propagation between the Spanish provinces. We also determine that the lockdown prevented the propagation of the virus within and between provinces. As such, the Spanish lockdown reduced the number of potential COVID-19 cases by 82.8%. However, the number of coronavirus cases would have been reduced by an additional 11.6% if the lockdown had been brought forward to March 7, 2020. Finally, an earlier lockdown would have saved approximately 26,900,000,000 euros.     

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

Effective Two-Level Domain Decomposition Preconditioners for Elastic Crack Problems Modeled by Extended Finite Element Method

In this paper, we propose some effective one- and two-level domain decomposition preconditioners for elastic crack problems modeled by extended finite element method. To construct the preconditioners, the physical domain is decomposed into the "crack tip" subdomain, which contains all the degrees of freedom (dofs) of the branch enrichment functions, and the "regular" subdomains, which contain the standard dofs and the dofs of the Heaviside enrichment function. In the one-level additive Schwarz and restricted additive Schwarz preconditioners, the "crack tip" subproblem is solved directly and the "regular" subproblems are solved by some inexact solvers, such as ILU. In the two-level domain decomposition preconditioners, traditional interpolations between the coarse and the fine meshes destroy the good convergence property. Therefore, we propose an unconventional approach in which the coarse mesh is exactly the same as the fine mesh along the crack line, and adopt the technique of a non-matching grid interpolation between the fine and the coarse meshes. Numerical experiments demonstrate the effectiveness of the two-level domain decomposition preconditioners applied to elastic crack problems.     

Automated Delineation of the Normal Urinary Bladder on Planning CT and Cone Beam CT

PurposeTo quantify the volumetric effect of delineation variability when using manual versus semiautomated tools to contour the normal bladder on planning computed tomography (CT) and cone beam CT.MethodsFollowing research ethics board approval, 10 prostate cancer patients were selected. For each patient, one pretreatment cone beam CT (CBCT) was randomly selected from the first treatment week and registered to the planning CT (planCT). Model-based auto adaptation was used to delineate the outer bladder (OB) surface for the planCT. That contour was then propagated and manually adapted onto the CBCT. A second observer delineated OB for the planCT and CBCT using typical manual methods. These delineation procedures were repeated four times on each image set, with observers blinded to the previous contours. Metrics of volumetric, geometric, and overlap concordance were used to compare the manual and automated OB contours.ResultsThe mean pairwise difference between the manual and model-based planCT volumes was 4 cm³ (2%), and the model-based contours exhibited approximately half the observer variation of the manual ones (3 cm³, 2%). The mean of pairwise differences between the manual and propagated CBCT volumes was 13 cm³ (8%), but the propagated contours exhibited approximately half the observer related volume variation (11 cm³, 6%). Small CBCT bladder volumes displayed larger observer variation with manual methods (r², −0.640). Variability between the automated contours was significantly smaller than for the corresponding manual observations (P = .004 and .002, respectively). Metrics of three-dimensional overlap concordance indicated excellent agreement within and between the delineation methods. Automated CBCT contours were significantly smoother than the manual ones (surface sphericity index, 1.29 vs. 1.35; P = .03).ConclusionsVolumetric, geometric, and overlap metrics all indicated that planCT and CBCT automated OB contours fell within the range of manually delineated contours. The CBCT propagated contours were significantly smoother and associated with smaller intraobserver variability, compared with manual contours. Importantly, the findings from this research suggest that contour propagation may be more robust than manual delineation, especially in the presence of poor image quality.     

Subharmonic,Non-linear Fundamental and Ultraharmonic Imaging of Microbubble Contrast at High Frequencies

There is increasing use of ultrasound contrast agent in high-frequency ultrasound imaging. However, conventional contrast detection methods perform poorly at high frequencies. We performed systematic in vitro comparisons of subharmonic, non-linear fundamental and ultraharmonic imaging for different depths and ultrasound contrast agent concentrations (Vevo 2100 system with MS250 probe and MicroMarker ultrasound contrast agent, VisualSonics, Toronto, ON, Canada). We investigated 4-, 6- and 10-cycle bursts at three power levels with the following pulse sequences: B-mode, amplitude modulation, pulse inversion and combined pulse inversion/amplitude modulation. The contrast-to-tissue (CTR) and contrast-to-artifact (CAR) ratios were calculated. At a depth of 8 mm, subharmonic pulse-inversion imaging performed the best (CTR = 26 dB, CAR = 18 dB) and at 16 mm, non-linear amplitude modulation imaging was the best contrast imaging method (CTR = 10 dB). Ultraharmonic imaging did not result in acceptable CTRs and CARs. The best candidates from the in vitro study were tested in vivo in chicken embryo and mouse models, and the results were in a good agreement with the in vitro findings.