Progressive Failure Research Articles

Diagnosing AL and ATTR Amyloid Cardiomyopathy: A Multidisciplinary Approach.

Amyloidosis with cardiac involvement is a fatal disease leading to progressive heart failure. The most common forms of amyloidosis with cardiac involvement are light chain (AL) and transthyretin (ATTR) amyloidosis. To allow effective specific treatment for both forms, precise and early diagnosis is important. This review focuses on diagnostic approaches for AL and ATTR amyloidosis with cardiac involvement, including different strategies, the role of imaging and biomarkers and possible pitfalls.

Effect of Lisinopril on Glomerular and Tubular Injury in a Surgical Rat Model of Progressive CKD and Kidney Failure

Effect of Lisinopril on Glomerular and Tubular Injury in a Surgical Rat Model of Progressive CKD and Kidney Failure

TCT-286 Impact of Dual Antiplatelet Therapy on Secondary Revascularization due to Native Vessel Disease Progression vs Graft Failure After Coronary Artery Bypass Graft

TCT-286 Impact of Dual Antiplatelet Therapy on Secondary Revascularization due to Native Vessel Disease Progression vs Graft Failure After Coronary Artery Bypass Graft

NDRG1 regulates iron metabolism and inhibits pathological cardiac hypertrophy

BackgroundCardiac pathological hypertrophy, a pathological physiological alteration in many cardiovascular diseases, can progress to heart failure. The cellular biology underlying myocardial hypertrophy remains to be fully elucidated. While NDRG1 has been reported to participate in cellular proliferation, differentiation, and cellular stress responses, its role in cardiac diseases remains unexplored. Here, we investigated the role of NDRG1 in pathological hypertrophy. MethodCardiomyocyte-specific-NDRG1 knockout (KO) transgenic mice and NDRG1-AAV9 were used in mice. Angiotensin II (AngII) stimulation were applied to induce hypertrophy. Histological, molecular, and RNA-sequencing analyses were performed, and ferroptosis markers and iron levels were studied. We used co-IP and application of iron chelator to further studied the mechanisms of NDRG1 in cardiac hypertrophy. ResultsWe found that NDRG1 expression is decreased in pathological hypertrophy induced by AngII stimulation. Conditional knockout of NDRG1 in mouse cardiomyocytes led to progressive cardiac hypertrophy and heart failure. Cardiomyocyte-specific overexpression of NDRG1 via AAV9 significantly reversed AngII-induced ventricular hypertrophy and fibrosis. Mechanistically, NDRG1-deficient cardiomyocytes exhibited iron overload and increased ferroptosis, accompanied by elevated levels of reactive oxygen species (ROS) and lipid peroxidation. Subsequently, we confirmed the involvement of NDRG1 in regulating ferroptosis and iron metabolism in myocardial cells. Finally, we identified an interaction between NDRG1 and transferrin in cells. The iron chelator Dp44mT effectively reduced myocardial iron overload and ventricular remodeling induced by NDRG1 deficiency. ConclusionThese findings highlight NDRG1's critical role in iron metabolism and ferroptosis in cardiomyocytes, suggesting that NDRG1 or iron metabolism may serve as therapeutic targets for cardiac hypertrophy.

Nonlupus Full-House Nephropathy Presenting with Rapidly Progressive Glomerulonephritis, Hypertensive Emergency, and Heart Failure

Nonlupus Full-House Nephropathy Presenting with Rapidly Progressive Glomerulonephritis, Hypertensive Emergency, and Heart Failure

Rapidly Progressive Kidney Failure in a Patient with Longstanding Juvenile Dermatomyositis

Rapidly Progressive Kidney Failure in a Patient with Longstanding Juvenile Dermatomyositis

Laparoscopic peritoneal lavage – a new treatment strategy in spontaneous bacterial peritonitis and liver cirrhosis

Introduction Bacterial infections in cirrhotic patients represent a major clinical problem, occuring 4-5 times more frequently compared to the general population and increasing mortality by leading to acute on chronic liver failure, subsequent decompensation, and multiorgan failure. The study’s purpose is to determine the possibilities of laparoscopy in the treatment of spontaneous bacterial peritonitis with decompensated liver cirrhosis. Materials and methods A retrospective descriptive study was conducted on 82 patients diagnosed with liver cirrhosis and spontaneous bacterial peritonitis, who were admitted to the Constantin Tibirna Surgery department No2, Holy Trinity Municipal Clinical Hospital and the Scientific Research Laboratory of Hepatic Surgery, Nicolae Testemițanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova, between January 2012 and December 2021. Patients who underwent surgical drainage of the abdominal cavity by laparoscopy with postoperative peritoneal lavage with antibiotics were selected. All patients received standard treatment for the correction of liver function and complications of portal hypertension. The data were extracted from the medical records of the hospital archive, and the patient database was compiled. Data analysis was performed using simple statistical calculations. Results Positive ascitic fluid bacterial culture was in 29.2% (24 patients), while 70.7% (58 patients) had culture-negative ascites and peritonitis. The most frequent bacterial species was E. coli, present in 54.1% (13 patients). Mortality was 8.5% (7 patients) due to progressive liver failure. Recurrence of ascites and peritonitis at 1 month was 6.0% (5 patients). Conclusions The laparoscopic approach in spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis allows for better sanitation of the abdominal cavity, improves peritoneal absorption, and deserves establishment as clinical practice for patients with ascites and peritonitis and cirrhosis.

Genome-Wide and Transcriptome-Wide Association Studies on Northern New England and Ohio Amyotrophic Lateral Sclerosis Cohorts.

Amyotrophic lateral sclerosis (ALS) is an age-associated, fatal neurodegenerative disorder causing progressive paralysis and respiratory failure. The genetic architecture of ALS is still largely unknown. We performed a genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) to understand genetic risk factors for ALS using a population-based case-control study of 435 ALS cases and 279 controls from Northern New England and Ohio. Single nucleotide polymorphism (SNP) genotyping was conducted using the Illumina NeuroChip array. Odds ratios were estimated using covariate-adjusted logistic regression. We also performed a genome-wide SNP-smoking interaction screening. TWAS analyses used PrediXcan to estimate associations between predicted gene expression levels across 15 tissues (13 brain tissues, skeletal muscle, and whole blood) and ALS risk. GWAS analyses identified the p.A382T missense variant (rs367543041, p = 3.95E-6) in the TARDBP gene, which has previously been reported in association with increased ALS risk and was found to share a close affinity with the Sardinian haplotype. Both GWAS and TWAS analyses suggested that ZNF235 is associated with decreased ALS risk. Our results support the need for future evaluation to clarify the role of these potential genetic risk factors for ALS and to understand genetic susceptibility to environmental risk factors.

Progressive failure of frozen sodium sulfate saline sandy soil under uniaxial compression

The progressive failure characteristics of geomaterial are a remarkable and challenging topic in geotechnical engineering. To study the effect of salt content and temperature on the progressive failure characteristics of frozen sodium sulfate saline sandy soil, a series of uniaxial compression tests were performed by integrating digital image correlation (DIC) technology into the testing apparatus. The evolution law of the uniaxial compression strength (UCS), the failure strain, and the formation of the shear band of the frozen sodium sulfate saline sandy soil were analyzed. The test results show that within the scope of this study, with the increase of salt content, both the UCS and the shear band angle initially decrease with increasing salt content before showing an increase. In contrast, the failure strain and the width of the shear band exhibit an initial increase followed by a decrease in the samples. In addition, to investigate the brittle failure characteristics of frozen sodium sulfate saline sandy soil, two classic brittleness evaluation methods were employed to quantitatively assess the brittleness level for the soil samples. The findings suggest that the failure characteristics under all test conditions in this study belong to the transition stage between brittle and ductile, indicating that frozen sodium sulfate saline sandy soil exhibits certain brittle behavior under uniaxial compression conditions, and the brittleness index basically decreases and then increases with the rise in salt content.

Bearing performance and progressive failure analysis of bolted joint in 3D printed pseudo-woven CFRP composite with fibre steering

This study investigates the bearing failure process of 3D printed pseudo-woven carbon fibre reinforced polymer (CFRP) composite joints, with a particular focus on the damage mechanisms influenced by steered fibres. A multiscale finite element model employing LaRC05 failure criteria is developed and validated against the experimental load–displacement curves and micro-computed microtomography (CT) images of four distinct cases. The model clearly demonstrates the critical importance of maintaining fibre continuity around the bolt hole, as this significantly influences the ability to reduce stress concentrations caused by the direct bearing loads from the bolt. Moreover, the model reveals that fibre steering can substantially improve the composite joint’s performance. This enhancement is achieved by adjusting the level of shear-induced damage propagation in individual filaments. The results demonstrate the potential and capability of the model to capture individual filament behaviour for the failure analysis of 3D printed composites, achieving good correlations with experimental measurements and observations, in terms of failure modes and load-bearing capacities.

Investigation of the notch sensitivity of tailorable long fiber discontinuous prepreg composite laminates

Tailorable discontinuous fiber composite laminates provide relative formability beyond that of continuous fiber laminates, while achieving improved mechanical performance over comparable stochastic systems. In this work, the notch sensitivity of engineered prepreg platelet molded composite (PPMC) laminates is investigated using the open-hole tension (OHT) test and compared to available data for stochastic PPMCs and continuous fiber laminates made with the same material. The press-formed thermoplastic composites (AS4/PEKK) were molded with a quasi-isotropic stacking sequence. The discontinuous PPMC laminate was found to be notch insensitive with OHT strengths ranging from 145.4 MPa (CV = 7%) for d/w=0.5 to 229.3 MPa (CV = 9%) for d/w=0.25. The highly ordered meso-structure of the engineered PPMC laminate yields comparatively excellent mechanical properties for relatively thin laminates in contrast to stochastic systems. Both net- and gross-section failures were observed for d/w=0.25, which suggests that the engineered PPMC laminates studied here maintain a degree of inherent, internal stress concentrations that compete with those caused by geometric features such as a circular hole. Computational simulations of the OHT tests with explicitly represented platelets were found to be in good agreement with experimental measurements. The progressive failure analysis was used to conduct a numerical investigation of the stacking sequence and platelet meso-morphology.

Cultural Consciousness and Gender Identity in Moses Ascending and Moses Migrating

Samuel Selvon’s literature lays emphasis on the development of a consciousness that moulds the entire issue of identity into a new shape. His literature comprises the story of West Indian immigrants in London and through his central characters, one can learn about Caribbeans’ realities in England. The arrival of commonwealth subjects in England after World War II was considered, by the protagonists as well as other characters in Selvon’s novel, as a possibility to form positive inter-racial relations to cope with the problems of decolonization, yet it signals the progressive failure of such possibility. His protagonists are subjected to cultural consciousness, existential struggle, crime, gender issues, love and hate, betrayal and death that lurk behind the city’s glimmer. Samuel Selvon outlines how their experiences and action influence the formation process of their identity and defines their behavior. This research paper endeavors to explore the cultural consciousness shared by Selvon’s protagonists as well as the issue of gender identity experienced by them, also aims to analyze the experience of exile commonly shared by Selvon’s main characters.

Progressive failure characteristics of coal under uniaxial compression: A comprehensive application of micro-ct and digital volume correlation

Progressive failure characteristics of coal under uniaxial compression: A comprehensive application of micro-ct and digital volume correlation

Progressive Failure of Water-Resistant Stratum in Karst Tunnel Construction Using an Improved Meshfree Method Considering Fluid–Solid Interaction

An improved meshfree method that considers cracking, contact behaviour and fluid–solid interaction (FSI) was developed and employed to shed light on the progressive failure of the water-resistant stratum and inrush process in a karst tunnel construction. Hydraulic fracturing tests considering different scenarios and inrush events of the field-scale Jigongling karst tunnel in three scenarios verify the feasibility of the improved meshfree method. The results indicate that the brittle fracture characteristics of the rock mass are captured accurately without grid re-meshing by improving the kernel function of the meshfree method. The complex contact behaviour of rock along the fracture surface during inrush is correctly captured through the introduction of Newton’s law-based block contact algorithms. FSI processing during inrush is accurately modelled by an improved two-phase adaptive adjacent method considering the discontinuous particles without coupling other solvers and additional artificial boundaries, which improves computational efficiency. Furthermore, the improved meshfree method simultaneously captures the fast inrush and rock failure in the Jigongling karst tunnel under varying thicknesses and strengths of water-resistant rocks and sizes of karst caves. As the thickness and strength of water-resistant rock increase, the possibility of an inrush disaster in the tunnel decreases, and a drop in the water level and an increase in the maximum flow velocity have significant delayed effects during the local inrush stage.

Urinary Growth Differentiation Factor 15 May Be a New Biomarker of Kidney Failure Progression in Diabetic Kidney Disease

Urinary Growth Differentiation Factor 15 May Be a New Biomarker of Kidney Failure Progression in Diabetic Kidney Disease

PCSK9 inhibitor attenuates cardiac fibrosis in reperfusion injury rat by suppressing inflammatory response and TGF-β1/Smad3 pathway

Progressive cardiac fibrosis, a hallmark of heart failure, remains poorly understood regarding Proprotein convertase subtilisin/kexin type 9 (PCSK9) ’s role. This study aims to elucidate PCSK9′s involvement in cardiac fibrosis. After ischemia/reperfusion (I/R) injury surgery in rats, PCSK9 inhibitors were used to examine their effects on the transforming growth factor-β1 (TGF-β1)/small mother against decapentaplegic 3 (Smad3) pathway and inflammation. Elevated PCSK9, TGF-β1, and Smad3 levels were observed in cardiac tissues post-I/R injury, indicating fibrosis. PCSK9 inhibition reduced pro-fibrotic protein expression, protecting the heart and mitigating I/R-induced damage and fibrosis. Additionally, it ameliorated cardiac inflammation and reduced post-myocardial infarction (MI) size, improving cardiac function and slowing heart failure progression. PCSK9 inhibitors significantly attenuate myocardial fibrosis induced by I/R via the TGF-β1/Smad3 pathway.

Dynamic Progressive Failure Analysis of 3D Five-directional Braided Composites under Transverse Compression Based on Macro-scale Heterogeneous Model

At present, there are few systematic researches on macro-scale heterogeneous modeling and numerical simulation of dynamic mechanical properties of 3-D braided composites. In this paper, the parametric virtual simulation model of 3D five-directional braided composites is realized in the way of “point-line-solid” based on the integrated design idea of process-structure-performance. And the impact compression numerical simulation of the material is carried out by using multi-scale analysis method. The effects of strain rate and braiding angle on transverse impact compression properties and fracture characteristics of composites is studies and verified by comparing the test results with the numerical simulation results systematically. The dynamic failure mechanism of the matrix and fiber bundles during the impact compression process is revealed. The results show that the macro-scale heterogeneous simulation model of 3D five-directional braided composites established is effective, and the numerical simulation results agree well with the test results. The matrix fracture and shear failure of fiber bundles are presented simultaneously under transverse impact compression. The failure of fiber bundles and matrix mainly concentrates on two main fracture shear planes. And the included angle between the fracture shear planes and the vertical direction is consistent with the corresponding internal braiding angle of specimens.

A study of the nonlinear behaviour of the irregular Beni Haroun cable-stayed bridge to progressive seismic failure under SVGM

The progressive failure of the nonlinear irregular Cable-Stayed Bridges (CSBs) under Spatial Variability of Ground Motions (SVGM) counting seismic wave propagation, incoherence effect and site-response effect is investigated. A spectral representation method is used in order to develop a computer code. This code is used to simulate SVGM time histories to be compatible with an overall coherency function and a target response spectrum, A three-dimensional Finite Element Model (FEM) of an asymmetric bridge: the Beni Haroun cable-stayed bridge (CSB) (North Eastern Algeria) is developed in order to include the effects of the main components of SVGM on response parameters in terms of variations of absolute maximum vertical displacements and flexural moments a long the deck and on height of short and tall pylons of study CSB, in particular, nonlinear bridge response quantities are examined in terms of rotational ductility demands at the ends of the short and tall piers of the bridge under all components of SVGM. The numerical results are comforted with those obtained assuming uniform seismic excitations. The analysis results reveal, among others, that the bridge responses are very sensitive to the SVGM, with site-response effects being more critical for bridge response than those of incoherence components and wave propagation. As a general trend, it is showed that the assumption of uniform excitation results in much lower ductility demands on bridges than incoherence and site SVGM components and that the latter should be considered for the seismic response assessments and progressive seismic failure studies of irregular cable-stayed bridges.

Multiscale modelling of CFRP composites exposed to thermo-mechanical loading from fire

Carbon fibre reinforced polymers (CFRP) are prone to structural damage during extreme events such as fire. Typically, modelling the effect of fire on CFRP structures is carried out through mesoscale analysis to predict overall structural performance. In this study, Finite Element (FE) modelling has been conducted to investigate the effects of fire on CFRP specimens at both meso- and micro-scales. The mesoscale analysis informs the microscale analysis to examine the effects of fire on each constituent of the material. A comparison of thermal analysis at the meso- and micro-scales reveals less than a 6% difference in the predicted nodal temperature. For the first time, fire-induced progressive failure analysis has been conducted on the fibres, matrix, and fibre/matrix interface of representative plies within the composite laminates. Fibre breakage, matrix cracking, and interface debonding were accurately captured using representative volume element (RVE) models under thermo-mechanical loading, showing qualitatively excellent agreement with experimental data.

Reliability inference of a multicomponent stress-strength model for exponentiated Pareto distribution based on progressive first failure censored samples

Multicomponent stress-strength (MC-SS) analysis is crucial for risk management and decision-making in various fields such as engineering, manufacturing, and quality control. It helps in identifying vulnerable components and areas where improvements can enhance overall system reliability. A primary contribution of this research is the implementation of the progressive first-Failure censored (PFIF-C) scheme. This scheme offers a novel and efficient approach to time and cost censoring, surpassing many existing censoring schemes found in the literature. The current study investigates the issue of MC-SS reliability inference under PFIF-C from the exponentiated Pareto distribution. The reliability of the MC-SS system is considered under the condition that both stress and strength follow an exponentiated Pareto distribution with a common second shape parameter. The parameter estimates and reliability estimate of the MC-SS system is produced using the maximum likelihood and Bayesian procedures. The asymptotic confidence intervals and highest posterior density credible intervals for the MC-SS system reliability are produced. Bayesian estimates are yielded using Markov Chain Monte Carlo under both informative and non-informative priors, considering symmetric and asymmetric loss functions. In order to assess the efficacy of the suggested methodology, simulation analyses are conducted. According to the simulation data Bayesian estimates of the MC-SS reliability, employing both symmetric and asymmetric loss functions, consistently outperform maximum likelihood estimates in terms of estimated risks. In general, Bayesian estimates based on asymmetric loss function perform better than the other competing loss function. The procedure is further shown with one real-world data example about failure times of a specific software model to show how the recommended approach may be applied to assess the strength and stress of a multicomponent model.