Failure Model Research Articles

Experimental and numerical simulation of seismic behavior of reinforced concrete frames infilled with refractory straw blocks

Recent earthquakes have highlighted the vulnerability of infilled reinforced concrete structures due to the insufficient consideration of infill masonry walls' contribution to strength and stiffness. This study presents a novel refractory straw block (RSB) designed to address these challenges and improve the seismic performance of reinforced concrete (RC) frames. Unlike traditional infills, RSB is characterized by low-elastic-modulus, low-density, and high-ductility. Quasi-static tests were performed on three types of frames: unfilled, infilled hollow grouted bricks (HGB), and infilled RSBs. Failure model, stiffness, and load-displacement response of three specimens were investigated and analyzed. The results indicate that RSBs as infill material does not alter the failure mode and constitutive relationship of bare frame, while HGBs leads to shear failure. The peak load for the specimen IF-HGB was 69.3 kN at 1.1 % drift, compared to 38.8 kN at 2.4 % drift for the specimen IF-RSB, and 36.4 kN at 2.0 % drift for the specimen BF. The strengths of specimens IF-HGB and IF-RSB were 1.90 and 1.07 times that of specimen BF, respectively. The stiffness of specimen IF-HGB was 3.7 times that of the other specimens, but its allowable displacement was only 61 % of theirs. Dynamic time-history analyses were also performed on structures with no longitudinal infill (BF), with RSBs (SBF), and with fired bricks (FBF). At the design level of rare events (magnitude 8, PGA 400 gal), severe damage occurred, but collapse was limited. When the PGA increased further, the collapse probability of model FBF rose rapidly, whereas the collapse probabilities of models SBF and BF remained low and similar. Accounting for the confining effect of walls, model FBF showed a higher probability of severe damage than models SBF and BF, particularly under minor earthquakes. The maximum inter-storey drift ratio of the model SBF and FBF were respectively 1.2 times and 1.7 times that of the model BF, which shows that straw blocks as infill can greatly avoid the effect of infill on the seismic behavior of the structure. The study also emphasized the often-overlooked confining effect of masonry on columns, which can lead to unrealistic damage assessments and seismic shear force distributions.

Interfacial interaction mechanism and theoretical bond strength model between UHPC-CA and steel bar

The bond property is the basis of the bear collectively load between the steel bar and Ultra-High Performance Concrete with Coarse Aggregate (UHPC-CA). In this paper, the theoretical calculation method of bond strength between UHPC-CA and high-strength steel bar is studied. The chemical adhesion strength, friction coefficient, and mechanical interlock process of the two were investigated respectively through the refined bond property tests. The failure model is established from the interlock failure characteristics, and the bond strength is obtained theoretically. Results show that the chemical adhesion strength and friction coefficient between UHPC-CA and steel bars are 0.07MPa and 0.5, respectively. The friction coefficient between UHPC-CA is 1.15. The interlock failure process of UHPC-CA and steel bars can be divided into three stages: uncracked stage, crack development stage, and split stage. The crack develops at an angle of 52° to the steel bar's axis and tends to stagnate at a height of 4.5 times the rib. A theoretical bond strength model is established and it is proved that the model is applicable not only to UHPC-CA but also to UHPC. This study can provide a theoretical basis for determining the anchorage length of steel bars in the design of UHPC-CA/UHPC structure, and can also provide a reference for the formulation of relevant standards.

ERBB4 activation prevents microvascular dysfunction in a large animal model of hypertensive heart disease

Abstract Background Coronary microvascular dysfunction (CMD) participates in the pathophysiology of multiple cardiovascular diseases, but treatment options are limited. A new treatment option may include ERBB4 stimulation by neuregulin-1 (NRG1), which has anti-inflammatory, antifibrotic, and cardioprotective effects in models of heart failure. Objectives To assess the effect NRG1/ERBB4 stimulation on CMD in hypertensive heart disease. Methods Hypertensive heart disease was induced in 12 Aachener minipigs by implantation of deoxycorticosterone acetate (DOCA) pellets for 8 weeks and compared to 6 controls. The DOCA pigs were randomized to a weekly infusion of JK07, a NRG1 fusion protein with improved pharmacokinetic and pharmacodynamic properties, or vehicle. Microvascular resistance was measured using the bolus thermodilution method. Results DOCA significantly increased microvascular resistance compared to controls (from 14.5 to 19.9 mmHg.s, p = 0.028). This increase was abrogated by JK07 (11.3 mmHg.s, p = 0.018 vs DOCA). dP/dtmax increased by DOCA compared to controls (from 2415.5 to 4455.5 mmHg/s, p = 0.011), which was also abrogated by JK07 (3107.3 mmHg/s, p = 0.055 vs DOCA). Interstitial left ventricular fibrosis was significantly lower in JK07-treated pigs compared to DOCA only (2.1 vs. 5.4 %, p = 0.026), but without difference in perivascular fibrosis (p = 0.48). JK07 did not affect myocyte cross-sectional area, capillary density, pericyte coverage, or microvascular vessel thickness. Conclusions ERBB4 activation by JK07 is capable to prevent CMD in a DOCA hypertensive pig model. Functional rather than structural alterations may explain the protective effects of JK07 on microvascular resistance.Visual summaryJK07 decreases microvascular resistance

Obesity plays a key role in inducing myocardial and vascular dysfunction in a translational model of heart failure with preserved ejection fraction in rats

Abstract Background Exploring experimental models of heart failure with preserved ejection fraction (HFpEF) may help to understand the mechanisms leading to this challenging condition. Purpose In a translational model, we aimed to assess the relative contribution of hypertension and obesity in inducing structural, functional and hemodynamic changes associated to the HFpEF phenotype. Methods We investigated 3 groups of male 40 weeks old rats: control Wistar Kyoto (WKY, n=10), Spontaneous Hypertensive Rats (SHR, n=10) and SHR with obesity induced by consumption of cafeteria diet during 28 weeks (Ob-SHR, n=9). Animals were submitted to assessment of: body weight, systolic (SBP) and diastolic (DBP) blood pressure; in vivo structural and functional changes evaluated by high resolution Echocardiography including left atrial dimension (LA), left ventricle (LV) diastolic dimension (LVDD), LV posterior wall thickness (LVPW), LV wall relative thickness (LVWRT), LV ejection fraction (LVEF). Invasive hemodynamic evaluation assessed the intraventricular pressure curves obtaining LV end diastolic pressure (LVEDP) and calculation of LV diastolic time constant (Tau). After euthanasia, thoracic aorta was used for vascular function assessment by measuring the maximal cumulative concentration-effect curves of contraction to phenylephrine (PE), expressed as Emax (%). Protein expression of Intercellular Adhesion Molecule 1 (ICAM-1) was determined in myocardial tissue (% in relation to WKY). Results were expressed as mean ± SEM and effects of groups vs time were compared with mixed ANOVA. Results The results are shown in the table. We observed higher levels of SBP and DBP in SHR and Ob-SHR when compared to WKY, but with similar values between SHR and Ob-SHR groups. Regarding the structural LV changes, we observed LV remodeling and LA dilation in both SHR and Ob-SHR groups, but with no difference between both hypertensive groups. The Ob-SHR was the only group showing increased LVEDP in comparison to other groups. The Tau was also increased in the Ob-SHR animals. Concordantly, the Ob-SHR group showed increased expression of ICAM-1 (figure - A) that was concomitant to abnormal vascular response with increased contraction to PE (figure - B) as compared to SHR and WK groups. Conclusions In this translational model of HFpEF in rats, the structural changes related to LV remodeling were similar in SHR and Ob-SHR, probably reflecting comparable higher levels of blood pressure observed in both groups. In contrast, elevated EDP, a hallmark of HFpEF, was only seen in the Ob-SHR group and this was concomitant to diastolic dysfunction, endothelial inflammatory activation and altered vascular function. Our results indicate that obesity is a key factor inducing vascular and myocardial changes that triggers HFpEF phenotype in this model.

Risk prediction models for incident heart failure: a systematic review and meta-analysis

Abstract Background Heart failure (HF) risk prediction models combine multivariable patient data to estimate an individual's risk of developing HF. By detecting at-risk and early-stage patients, models may facilitate earlier intervention to prevent or delay HF development. Previous systematic reviews were unable to recommend any existing prediction models for clinical use due to insufficient evidence and lack of guidelines on appraising study quality at their time of publication. Purpose To summarize the performance of risk prediction models for incident HF and identify models for further validation and potential clinical use. Methods We searched MEDLINE and EMBASE in June 2021 for English-language studies developing or validating HF risk prediction models. Studies were also retrieved from two previous systematic reviews. We narratively summarized model characteristics (e.g. model type, predictors used, prediction horizon) and study methodology (e.g. validation methods). Performance was assessed among all models validated in ≥ 1 cohort. For all models validated in ≥ 2 cohorts, we pooled discrimination measures using random-effects meta-analyses. Calibration was descriptively summarized based on individual study results from statistical tests and graph digitization of calibration plots. Study quality was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Results Of 18,937 publications screened, 41 studies consisting of 120 prediction models were included. Twenty models were both derived and validated, 99 only derived, and 1 only validated. Risk of bias was rated as high in nearly all (94.7%) PROBAST assessments, mostly attributable to issues with analysis. Among 21 models validated in ≥ 1 cohort, most had moderate (61.9%, C-statistic 0.7 to <0.8) or high (23.8%, C-statistic 0.8 to <0.9) discrimination. In patients with low predicted risk (<10%), the calibration was adequate. Nine (42.9%) of these 21 models were presented as web-based calculators and five (23.8%) as points-based risk scores. Based on performance, number of validation cohorts, study risk of bias, and user friendliness, the Atherosclerosis Risk in Communities (ARIC), Multi-Ethnic Study of Atherosclerosis (MESA), Pooled Cohort equations to Prevent Heart Failure (PCP-HF), and Health ABC models emerged as the most promising risk scores for clinical practice. Conclusions Given their acceptable performance but high risk of bias, future studies should focus on the external validation of these models in studies of high methodological rigor. Models should be validated in a greater diversity of patient populations, particularly with respect to race. Impact analyses assessing how the clinical implementation of these models affects patient outcomes are also required prior to their routine use. Once validated, these models may help guide clinical decision making to prevent the onset of HF with early, aggressive risk factor modification.Discrimination in 21 validated modelsCharacteristics of recommended models

Long-term outcomes after transcatheter aortic valve implantation: derivation and validation of the long-TAVI prediction model

Abstract Background Identification of high-risk individuals after transcatheter aortic valve implantation (TAVI) is essential to personalized care. Established risk models require a plethora of variables, fail to account for biomarker dynamics and imaging parameters, mostly focus on the short term, and offer limited predictive performance. Purpose We aimed to develop an easily applicable prediction model for long-term mortality or heart failure (HF) admission following TAVI. Methods Patients undergoing TAVI at a high-volume university centre in the United Kingdom (n = 990) were recruited into a prospective cohort study. Enrolled patients were divided into a development cohort (07/2007 – 12/2016) and a validation cohort (01/2017 – 11/2018) and followed for up to 15.1 (median 5.3, interquartile range [IQR] 2.8 – 7.4) years. Patient characteristics along with pre- and post-procedural imaging results and brain natriuretic peptide (BNP) levels before the procedure and at 3 months were recorded. A clinical risk score for long-term mortality and HF admission (i.e., Long-TAVI risk score) was derived using Cox regression and evaluated using time-dependent area under the receiver operating characteristics curve (AUC). Results Age at presentation was 79.8 (standard deviation [SD] 8.9) years, 961 (99.0%) patients had signs of heart failure, left ventricular ejection fraction was 52 (SD 11.2), and pre-TAVI BNP levels were 298.0 (interquartile range [IQR] 159.0 – 571.5) pg/mL. High BNP levels at presentation (higher vs. lower than 400 pg/mL: HR 1.50, 95% CI 1.17 – 1.92, P < 0.001) and dynamic changes in BNP with the first 3 months (low/high vs. low/low: 2.61, 95% CI 1.17 – 5.86, P = 0.020; high/high vs. low/low: 2.41, 95% CI 1.26 – 4.64, P = 0.008) were independent predictors mortality or HF admission. The simple 8-item Long-TAVI score accounts for periprocedural BNP dynamics and shows good discrimination (AUC 0.76, 95% CI 0.72 – 0.79) and calibration in the development cohort performing similarly well in the external validation cohort (AUC 0.70, 95% CI 0.63 – 0.77). Long-TAVI significantly outperformed the logistic EURO score (AUC 0.56, 95% CI 0.52 – 0.59, P < 0.001). Conclusion Both pre-TAVI BNP levels and periprocedural BNP trajectories are independently associated with long-term outcomes after TAVI. Accounting for clinical characteristics, imaging parameters, and circulating BNP levels, the newly developed Long-TAVI risk score achieves high performance and provides the first prediction model for long-term mortality or HF admission. Long-TAVI represents a novel tool for personalized risk assessment in patients undergoing TAVI.Correlation at baseline A) and FUP B)Score performance A) and risk groups B)

Vaccination targeting senescence-associated transmembrane protein alleviated cardiovascular pathology in the mice

Abstract Introduction Accumulation of senescent cells is observed in various organs including vasculature, heart and white adipose tissue with age, and known to become a substrate of pathophysiology of various cardiovascular-metabolic diseases. We have previously developed a vaccine to eliminate senescent cells, so-called "senolytic vaccine" by targeting Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) as a cellular-senescence-associated cell surface protein. We have demonstrated that GPNMB senolytic vaccine could remove senescent cells and alleviate the pathology cardiovascular-metabolic diseases. Senescence-associated adhesion molecule 1 (SAAM-1) is also known as a cell-surface membrane to increase its expression during cellular senescence in endothelial cells as well as the development of cardiovascular diseases. Here, we identified SAAM-1 as another senescence antigen and created a vaccine to eliminate senescent cells by targeting SAAM-1. Purpose This study was purposed to evaluate the efficacy of SAAM-1 vaccine for the treatment of cardiovascular diseases in mice models. Methods As a pressure overload-induced heart failure (HF) model, C57BL/6N wild type (WT) mice were underwent transverse aortic constriction (TAC) or sham opretaion at 13 weeks of age. SAAM-1 or control vaccination were given at 8 and 10 weeks of age before operation. Echocardiography examination was conducted two weeks after TAC operation, followed by tissue sampling 3 weeks after the examination. As an atherosclerosis model, ApoE KO mice were subjected to a high-fat diet (HFD) starting at 4 weeks of age. Vaccination of ApoE KO mice was administered at 8 weeks of age with SAAM-1-vaccine or control-vaccine, followed by sacrifice 4 weeks later for further analysis. ApoE-KO mice were also crossed with p16-mediated Luciferase expressing mice (p16-Luc mice) and subjected to generation of atherosclerosis model. Results SAAM-1 expression was significantly increased in left ventricle (LV) in TAC mice but its increase was suppressed by SAAM-1 vaccination. Interestingly, both worsening systolic function and dilatation of LV by pressure overload were significantly alleviated by SAAM-1 vaccination. Furthermore, expression level of senescent markers including p16 and p21, as well as several inflammation markers were increased in failing heart along with development of cardiac fibrosis, but SAAM-1 vaccine could significantly attenuate this pathological change. In ApoE KO mice, SAAM-1 vaccine decreased expression level of several inflammation markers in the mice, along with a decreasing p16 signal in the aorta. Conclusions Targeting SAAM-1 for vaccination would be a novel and promising approach to alleviating age-related cardiovascular disease.

Eicosanoids in coronary sinus negatively correlate with natriuretic peptides in heart failure with reduced ejection fraction: insights from Eicosanoids in Human Heart Failure Study

Abstract Background The diagnostic and therapeutic potential of eicosanoids, metabolites of arachidonic acid with positive cardio-renal activity in preclinical heart failure models, remains unclear in human chronic heart failure with reduced ejection fraction (HFrEF). Purpose The aim of this part of a traslational Eicosanoids in Human Heart Failure Study was to investigate levels of eicosanoids in different body compartments and their relation to natriuretic peptides. Methods Eleven consecutive patients with HFrEF indicated to cardiac resynchronisation therapy (CRT) were enrolled to measure plasmatic 14,15-epoxyeicosatrienoic acid (14,15-EET) and 14,15-dihydroxyicosatrienoic acid (14,15-DHET) levels from venous, arterial, and coronary sinus (CS) blood samples and correlate them with N-terminal pro B-type natriuretic peptide (NT-proBNP) from the same compartments. Results In CS, NT-proBNP levels negatively correlated with plasmatic 14,15-EET levels (r = -0.63, p = 0.03) and positively with the DHET/EET ratio (r = 0.73, p = 0.02). This correlation was not found in the other compartments. Plasmatic 14,15-EET nor 14,15-DHET levels in measured compartments did not differ statistically (p = 0.21, p = 0,64, respectively). In individual patients, the levels of both eicosanoids correlated across all compartments. Peripheral plasma 14,15-EET levels in controls were lower compared to HF patients. Conclusion Peripheral venous eicosanoid (14,15-EET, 14,15-DHET) levels correlate and do not differ from arterial and CS levels in patients with HFrEF indicated to CRT. In CS, NT-proBNP levels negatively correlated with plasmatic 14,15-EET levels and positively with the DHET/EET ratio, an indirect soluble epoxide hydrolase activity parameter.Graphical AbstractFigures

Exploring vocal biomarkers as non-invasive fine-tuning assays of cardiovascular health: heart failure model

Abstract Background Mobile health (mHealth) technologies offer a promising avenue for non-invasive heart failure monitoring through vocal biomarkers. The relationship between feature changes in anonymous and standardized voice recordings of heart failure patients and the NYHA scores of the same patients is assessed, aiming to identify vocal biomarkers as delicate indicators of chronic noncommunicable disease progression and/ or fluctuation. Methods In a cardiology outpatient setting, 55 chronic heart failure patients provided voice recordings via a mobile app, performing specific vocal tasks prospectively. We analyzed waveforms visually via Mel spectrograms and extracting features by audio processing, focusing on chroma centroids and tonnetz measurements across 147 clinical and laboratory parameters (Mean NYHA: 2.62, SD: 0.56). Applying Ordinary Least Squares (OLS) test, we assessed the relevance of spectral bandwidth mean (0.04), spectral bandwidth std (0.00), spectral roll-off std (0.011) between NYHA scores, given each p-score < 0.05. Results 147 voice recordings taken from 55 patients were analyzed to examine whether there were any correlations between changes in the voice recordings and NYHA scores. OLS test underscored the significance of spectral bandwidth mean (0.04), spectral bandwidth std (0.00), spectral roll-off std (0.011) between NYHA scores with p-value < 0.05. These findings show the potential role of multiple vocal features in reflecting heart failure progression and/or fluctuation. Analysis based on the clinical status progression from NYHA 2 to NYHA 3 over time showed notable changes in chroma centroids (mean = 0.006, std = 0.174, skew = 0.179, kurtosis = 0.205) and tonnetz (mean = 0.023, std = 0.131, skew = 0.023, kurtosis = 4.247). Conclusion This investigation highlights vocal biomarkers' potential in heart failure management, offering insights into non-invasive monitoring techniques and shows the importance of standardised recording procedures and patient engagement for data integrity. Future directions include quantifying vocal changes' correlation with clinical status and integrating additional parameters (e.g., edema, weight) to enhance predictive models for personalised care.Vocal features according to NYHA scores

Overload cascading failure detection algorithm for multi-layer supply chain network considering delay probability factor

At present, the supply chain is multi-layered and complicated, and its failure detection is based solely on the characteristic threshold, which does not lack the ability to describe the complex supply chain. An overload cascading failure detection algorithm for multi-layer supply chain network considering delay probability is proposed. Based on the multi-layer supply chain network including raw material suppliers, manufacturers, distributors and retailers, the overload cascading failure model of the multi-layer supply chain network is constructed through networking, and the overload cascading failure process of the multi-layer supply chain network is described through three aspects: initial load, node capacity and overload node load distribution. By monitoring and analyzing the status update messages of each node in the supply chain network, and considering the delay probability factor, the node and path that may lead to cascading failure are identified by predicting the delay probability of the next message through the historical message delay probability, and the overload cascading failure detection of the multi-layer supply chain network is realized. The experimental results show that the algorithm can effectively detect the failure of each overloaded enterprise node in the multi-layer supply chain network, which is helpful to enhance the early warning and response ability of the cascade failure of the supply chain network. The algorithm can realize the failure detection of supply chain network under different attack conditions and initial failure ratio of nodes, and measure the anti-risk ability of supply chain network. Under deliberate attack and when the initial attack node is a supplier network layer node, it has a greater impact on the multi-layer supply chain network.

Failure analysis of multi-span masonry arch bridges using combination of point cloud data and three-dimensional numerical modeling

Historical structures, including historical bridges, are part of cultural heritage, conveying the traces and characteristic features of past civilizations. To protect historical structures, it is necessary to prepare their 3D photogrammetric documentation, determine detailed geometric and material properties and perform computer-aided structural analysis using appropriate modeling techniques. The aim of this study is to present an effective, reliable and fast multidisciplinary approach for the analysis of historical masonry bridges. The aforementioned approach was illustrated with an example of the historical Halilviran masonry arch bridge and its behavior under possible loadings. Terrestrial laser scanning (TLS) was used to determine the bridge geometry with high accuracy. Point cloud data obtained from TLS was simplified and a three-dimensional CAD-based solid model of the structure was created. The Halilviran Bridge case study summarized in this report was conducted to examine the technical feasibility of using la¬ser scanning technologies for obtaining as-built records for similar historic bridges. A secondary objective was to identify other applications of this technology, notably for other transportation structures, and use numerical methods to assess the seismic behavior and failure model of the bridge. The seismic behavior of the bridge was examined using a finite-element- based macromodeling technique. Nonlinear dynamic analyses were carried out subsequently to identify the most susceptible regions of the bridge. Interpretation of the results, presented in the form of contour plots illustrating tensile damage and maximum displacements, offered a comprehensive depiction of the seismic response across the entire bridge. The methodology employed in this investigation can be viewed as a robust framework for evaluating the seismic response and potential failure of historical structures.

Resilience optimization analysis of smart mining cluster cyber-physical systems based on the NK model

This paper explores the challenges and opportunities presented by the digitization and intelligent clustering in the mining industry, focusing on the security and inter-system influences within Cyber-Physical Systems (CPS) of smart mining clusters. Utilizing the NK model and complex adaptive systems theory, we construct a dual-layered network and cascade failure model, alongside a dynamic repair strategy that adapts to environmental changes. By analyzing the critical parameters of node number (N) and relationship density (K), we assess the resilience of smart mining CPS under cascade failures with dynamic repairs. Our findings reveal that dynamic repair strategies significantly enhance network resilience against both random and deliberate attacks, with N and K acting as crucial regulators of repair effectiveness. This suggests that adapting N and K can improve repair outcomes and system resilience, despite increasing complexity. The paper discusses the practical implications of these strategies through simulation and real-world scenarios, highlighting the need for adaptive repair strategies in enhancing smart mining CPS resilience and process safety. Introducing the NK model to CPS resilience research offers new insights into the resilience of smart mining cyber-physical systems and provides a comprehensive risk analysis method for these systems in complex scenarios.

Quantitative assessment of congestion diffusion and cascading effect under rainfall-flood disasters: A case study of Nanjing, China

Urban road networks are frequently disrupted by flooding rainfall-flood disasters, which can cause severe traffic disruptions and leading to traffic congestion due to cascading effect. This paper investigates the reliability issues under rainfall-flood conditions. A coupled model, integrating a rainfall-flood model with an improved cascading failure model, is proposed to assess how rainfall intensities and flooding will influence traffic congestion and bring network instability. Utilizing an improved Nonlinear Load-Capacity model, we quantify the impact of congestion and analyze cascading processes under various rainfall-flood conditions. The case study in Nanjing, China reveal that, when congestion causes network pressure to exceed the traffic percolation threshold, traffic congestion diffusion becomes more pronounced, putting excessive strain on other passable roads. Network cascading failures due to traffic congestion diffusion can lead to excessive focus on the remaining passable roads, resulting in a sharp increase in the average importance. The significance of this work lies in its provision of an effective method for predicting potential network disruptions and cascading failures in advance, thereby enhancing post-disaster road operations.

A New Method for Determining the Safety Distance Between Irregular Karst Cave and Circumferential Shield Tunnel

ABSTRACTWhen a shield tunnel passes through a karst area, the water‐filled cave can easily make the surrounding rock metamorphic, resulting in water inrush, ground collapse, and shield machine failure and other engineering hazards. Natural cavities have a significant degree of geometric irregularity due to groundwater alteration and soluble rock erosion. Considering the difficulties in describing the shape of a natural irregular cavity, circular, rectangular, and elliptical geometries have been simplified in most related studies. Based on the upper bound theorem of limit analysis, we established a three‐dimensional failure model including the karst caves located directly above and below the circumferential side of the tunnel. Then, we deduced the corresponding analytical solution of the critical safety distance (CSD). Furthermore, the effects of rock mass parameters, cave parameters, and geometric parameters on the CSD were analyzed. Then we designed the numerical simulation considering the irregular geometry shape at the circumferential side of tunnel using the Fourier descriptors. In addition, we estimated the CSDs for two failure models using the revised dichotomy and failure criterion. The findings demonstrated a quantifiable association between CSD and Fourier descriptors of irregular cave shape, resulting in the development of a CSD prediction model. These test results can provide a theoretical foundation and direction for predicting water inrush caused by the constrained irregular cave.

The Variation of Several Parameters in the Premature Ovarian Failure Model by D-Galactose and the Effect of Some Drugs on the Model: Fundamental Study

The Variation of Several Parameters in the Premature Ovarian Failure Model by D-Galactose and the Effect of Some Drugs on the Model: Fundamental Study

Time-dependent reliability analysis of flood defenses under cumulative internal erosion

Internal erosion is a significant cause of failure in dams, levees and other hydraulic structures. This article studies the time-dependent reliability of such structures under Backward Erosion Piping (BEP), a form of internal erosion in the foundation. First, a physics-based time-dependent piping failure model is presented. Second, a time-variant reliability analysis method is presented which allows to quantify how the reliability evolves over the years due to cumulative pipe growth over multiple flood events. Finally, these models are used to study the importance of time-dependence for reliability estimates of flood defenses in The Netherlands. The findings show that, particularly in coastal areas, incorporating time-dependence significantly reduces the computed failure probability. Reductions vary widely, ranging from a factor of 5 to more than 10 6 , depending on flood duration and levee properties. Therefore, reliability estimates for levees can be improved by incorporating time-dependent pipe development in the BEP failure model, and thereby contribute to avoiding unnecessary reinforcements.

Cardiomyocyte myofilament function in common animal models of heart failure with preserved ejection fraction

Human cardiomyocytes from very obese patients with heart failure and preserved ejection fraction (HFpEF) have markedly depressed calcium-activated tension and increased resting stiffness. To test if either are recapitulated by obese-HFpEF animal models, tension‑calcium and tension-sarcomere length relations were measured in myocytes from mice on a high fat diet (HFD) with L-NAME, ZSF1 rats, and Göttingen minipigs on HFD + DOCA (MP). Only MP myocytes displayed reduced Ca2+-activated tension, and none exhibited increased resting stiffness versus respective controls. Consistent with prior myofibrillar data, crossbridge attachment and detachment rates at matched tension were slower in rodent models, and detachment slower in MP.

Calcium ATPase (PMCA) and GLUT-4 Upregulation in the Transverse Tubule Membrane of Skeletal Muscle from a Rat Model of Chronic Heart Failure.

Intolerance to exercise is a symptom associated with chronic heart failure (CHF) resulting in SM waste and weakness in humans. The effect of CHF on skeletal muscle (SM) arose from experimental evidence in rat models to explain the underlying mechanism. We investigated SM mechanical and metabolic properties in sham rats and with coronary ligation-induced CHF. After twelve weeks of CHF, rats were catheterized to measure right auricular pressure, SM mechanical properties, SERCA-ATPase activity and plasma membrane Ca2+-ATPase (PMCA) hydrolytic activity in isolated sarcoplasmic reticulum (SR) and transverse tubule (TT membrane), respectively, in the sham and CHF. The right auricular pressure and plasma nitrite concentration in CHF increased two-fold with respect to the sham. Pleural effusion and ascites were detected in CHF, confirming CHF. SERCA activity was conserved in CHF. In TT membranes from CHF, the glucose transporter GLUT4 increased seven-fold, and the PMCA hydrolytic activity increased five-fold, but in isolated muscle, the mechanical properties were unaffected. The absence of a deleterious effect of coronary ligation-induced CHF in the rat model on SM could be explained by the increased activity of PMCA and increased presence of GLUT-4 on the TT membrane, which may be involved in the mechanical outcome of the EDL.

Real-world safety profile of zanubrutinib: a disproportionality analysis based on the FAERS database

ObjectiveZanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor that has been approved for the treatment of several B cell malignancies. The aim of this study was to evaluate adverse events...

Contract labour in mining and occupational health and safety: A critical review

Abstract In recent decades, there has been a global growth of the use of contract labour in the mining industry, primarily driven by cost/flexibility considerations. At the same time, contracting has been associated with poorer occupational health and safety (OHS) outcomes across a range of industries. Drawing on published research, theses, and government reports, this paper critically reviews the available evidence on the OHS effects of contract labour in mining and the likely implications of further growth in this trend. This evidence confirms that the use of contract labour is associated with worse OHS outcomes, and that the Ten Pathways and Pressure, Disorganisation, and Regulatory failure (PDR) models are both valuable in explaining this. The latter point is confirmed by a more detailed examination of four serious mine incidents in NSW and Queensland. The paper identifies some gaps and areas for further research as well as the actions that mining companies, regulators, and unions could take to improve contractor safety. Notwithstanding the latter, the paper argues that the most effective way of improving contractor safety in mines is reducing the use of contractors overall and concentrating their activities in areas such as major shutdowns/repairs, where contractors have specialised expertise to undertake non-routine tasks. Despite oft-repeated phrases such as zero-harm and management systems, the corporate shift to using contractors is primarily driven by cost-cutting and highlights how OHS is compromised by such priorities.