Search Results (1,286)

Flexible automated assembly lines (FAALs) in Industry 4.0 require robust quality management that integrates operational data with systematic risk analysis. However, Process Failure Mode and Effects Analysis (PFMEA) documents are often developed during the design phase and not systematically updated with actual production data, leading to a gap between formal risk assessment and operational reality. This study addresses this gap by developing and validating an integrated data-driven framework that combines classical quality tools (process flow charts, check sheets, cause-and-effect diagrams, and Pareto analysis) with data-driven PFMEA, creating traceable links from operational logs to risk ratings. While individual quality tools are well-established, the core contribution of this work is a structured data transformation pipeline that creates traceable, auditable linkages from raw operational event logs to calibrated PFMEA ratings with quantified uncertainty—a combination not previously demonstrated for flexible assembly systems. The framework was applied to FMS-200, a modular FAAL for bearing units, consisting of eight stations and a common transfer system. Analysis of 186 failure events across 2743 assembly cycles, including 18 product configurations, identified 40 distinct failure modes with risk priority number (RPN) values ranging from 60 to 378, revealing that approximately 90% of the aggregated risk is associated with pneumatic systems. Monte Carlo uncertainty analysis (10,000 iterations) demonstrated robust rank stability, with the top five failure modes maintaining their relative ordering in over 90% of simulations. The framework provides production and quality managers with a systematic methodology to maintain PFMEA relevance through continuous data integration, enabling evidence-based prioritization of improvement actions. Full article

Background and Objectives: The interaction between the brain and heart has become more interesting in the last 20 years. The most common cardiac complications after stroke are myocardial infarction, heart failure, arrhythmias, electrocardiographic disturbances, repolarization disorders, and sudden cardiac death. The prolonged Tpeak–Tend interval is an indicator of the electrical heterogeneity of the myocardium (abnormal repolarization) that causes malignant arrhythmias. We aimed to investigate whether the Tpeak–Tend interval, which reflects the heterogeneity of repolarization, is prolonged in stroke and its relationship with short-term mortality. Materials and Methods: Individuals over the age of 18 who presented with hemorrhagic or ischemic stroke were included in the study. Demographic characteristics, laboratory and imaging findings of the patients were recorded. ECGs were obtained at the time of admission to the hospital and 24 h later. Patients were followed for in-hospital mortality. Results: 89 (82.4%) of the patients had ischemic stroke, 19 (17.6%) had hemorrhagic stroke. It was determined that Tp-eV2 and Tp-eV5 at hospital admission were significantly longer than the 24th hour values. A total of 92.01 (16.3) ms at Tp-eV2 admission, 84.1 (16.3) ms after 24 h (p = 0.003), 91.9 (7.3) msTp-eV5 at admission, and 81.6 (17.8) ms (p = 0.000) after 24 h. In multivariate logistic regression analysis of in-hospital mortality, Tp-eV2 (HR: 0.96 (95% CI 0.93–0.99) p = 0.008) was determined as an independent predictor among cardiovascular parameters. Conclusions: Tp-e intervals were prolonged in both leads V2 and V5 in patients with stroke. Prolongation of lead V2 in the Tp-e interval is an independent indicator of short-term mortality among cardiovascular parameters. Full article

Occupational Health and Safety systems, as well as physical Ergonomics, serve a common goal, which is to eliminate safety-related injuries within production systems. The analysis of potential hazards that could compromise the safety of operations’ employees assists in preventing a high rate of safety-related injuries. Safer processes result in a high output rate and, hence, a profitable business. Focusing on the accuracy of problem solving and failure prediction analysis on new processes could potentially result in zero safety-related injuries, good-quality products, cost reduction, and the elimination of delays within the processes. This research seeks to add more knowledge to the fields of Occupational Health and Safety systems and Total Productive Maintenance by combining lean manufacturing troubleshooting models with Ergonomic analysis, as well as Hazard Identification Risk Analysis, to predict future kaizen projects for businesses. The proposed upgrade to the problem-solving model was developed by evaluating and reviewing the impact of Ergonomic analysis on different production systems. It was found that Ergonomic analysis provides solutions for a more comfortable working environment; hence, the existing troubleshooting model was combined with an Ergonomic exercise. The proposed model is more beneficial to production systems. It could potentially result in zero safety-related injuries, high-quality products, more accurate problem analysis, and more innovation by enabling kaizen projects. The proposed model was applied in the electronics industry, where it resulted in drastic improvements. The old method, which was causing fatigue, was eliminated, and a new machine was designed and prototyped. The new machine assisted the company in this case study in reducing delays, eliminating defects, and reducing costs. Furthermore, the proposed troubleshooting model evaluated an impactful kaizen project, which was the introduction of new technologies that will eliminate the power-up stage. Full article

The operational reliability of Emergency Diesel Generators (EDGs) is paramount for the safety of nuclear power plants. This study investigates the fretting wear mechanism on the non-working back-face of connecting rod big-end bearings—a critical failure mode that can lead to catastrophic engine damage. A synergistic approach was employed, integrating theoretical pressure calculations, on-site strain measurement experiments, and high-fidelity non-linear finite element analysis (FEA). The results demonstrate that while the theoretical design back-face pressure ranges from 8.1 to 10.1 MPa, the actual pressure is highly sensitive to bolt preload. A 16.2% attenuation in preload (from 550 kN to 461 kN), common during maintenance cycles, causes the interfacial pressure to drop to 6.9 MPa, falling below the recommended safety threshold of 7 MPa required to inhibit fretting. Furthermore, comparative experiments reveal that used bearings exhibit significantly lower and less uniform radial pressure retention compared to new bearings, even when physical dimensions appear compliant. Dynamic FEA indicates that peak inertial loads induce an out-of-roundness (DOR) of 0.295 mm, triggering a transition from a “partial slip” to a “macro-slip” regime at the interface. The findings confirm that the coupling of preload attenuation and loss of bearing elasticity drives the fretting process, providing a theoretical basis for optimized maintenance and selective assembly strategies. Full article

Among cardiac storage diseases, amyloidosis has emerged as a common cause of heart failure (HF), particularly in older people: it is diagnosed in up to 13–19% of patients with heart failure and preserved ejection fraction. Current treatments for transthyretin amyloidosis (ATTR) focus on stopping the misfolding of the TTR protein or reducing TTR production and treating the symptoms with cardiac medication, while systemic chemotherapy is the focus for light-chain amyloidosis (AL). New fibril clearance agents and gene therapies are currently in development. In addition to clinical and laboratory observations, multimodal imaging is essential for the monitoring of the effects of treatment on the progression of heart disease, but it is not yet included in established staging systems. This narrative review collects current multimodal imaging parameters that have been evaluated in clinical trials to assess the progression of cardiac amyloidosis and used in phase III intervention studies. These evolving findings are compared with current consensus recommendations to identify gaps in knowledge for specific imaging modalities, particularly cardiac MRI. Ultimately, the goal should be to standardize imaging of disease progression in cardiac amyloidosis so that the therapeutic effects of new pharmacological treatment options can be compared with the current standard of care. Full article

Human reliability analysis of the human–computer interaction process between users and systems is critical because human error can introduce significant system risks. Interaction systems designed with human reliability analysis can reduce human error. This study proposed a research methodology for analyzing human error to design interactive systems that align with users’ cognitive demands. First, the cognitive reliability and error analysis method (CREAM) is used to investigate cognitive function failures and determine the nominal cognitive failure probability. Next, fuzzy comprehensive evaluation (FCE) is used to assess the level of common performance conditions (CPCs). Subsequently, the decision-making trial and evaluation laboratory (DEMATEL) method is employed to compute the factor centrality weights of CPCs and human intrinsic factors (HIFs). The interactions among CPCs are analyzed, leading to the determination of cognitive impact weights. Then, the cognitive failure probability is calculated by combining factor centrality weights and cognitive impact weights. Finally, error causes are analyzed to propose optimization strategies and implement design improvements. An in-vehicle information system was used to validate the proposed approach. The findings revealed that this method effectively minimizes cognitive failure probability during system interaction. It also identifies the causes of human error in human–computer interactions and offers a systematic strategy to enhance human reliability in interaction design. Full article

Background/Objectives: Congestion is a hallmark of heart failure (HF) and a major determinant of outcomes. Non-invasive tools enable detection of subclinical congestion, but their correlation and prognostic relevance remain incompletely defined. The present study aimed to assess the prevalence, evolution, interrelationships, and prognostic impact of clinical and subclinical congestion markers in patients hospitalized for HF. Methods: This single-centre, prospective cohort study included adults admitted with HF who underwent serial evaluations at admission, 72 h, pre-discharge, early outpatient follow-up and at 6 months. Clinical congestion was assessed using a standardized physical examination score. Subclinical congestion was evaluated using lung ultrasound (LUS), Venous Excess Ultrasound Score (VExUS), and Remote Dielectric Sensing (ReDS). Patients were classified according to the presence of clinical and/or subclinical congestion at discharge. The primary endpoint was a composite of all-cause mortality, HF readmission, or unscheduled visits requiring intravenous diuretics within six months. Results: Ninety-four patients (mean age 74 ± 11 years, 68% male) were included. While clinical congestion improved significantly during hospitalization, approximately 30% of patients remained clinically congested at discharge. Among clinically euvolemic patients, only 47% showed no evidence of subclinical congestion. Correlations between congestion markers were weak to moderate, suggesting complementary pathophysiological information. At discharge, pulmonary B-lines were the strongest predictor of the composite endpoint (hazard ratio [HR] 3.50, 95% CI 1.41–8.72), followed by clinical congestion (HR 2.67, 95% CI 1.13–6.30). Patients with clinical and subclinical congestion exhibited lower event-free survival. Conclusions: Subclinical congestion is common despite apparent clinical euvolemia and is associated with worse outcomes. Integrating clinical assessment with non-invasive congestion markers may improve post-discharge risk stratification in HF. Full article

Background: Genetic causes of growth failure should be suspected in patients born small for gestational age (SGA) who fail to show postnatal catch-up growth, present with severe short stature (SS), and exhibit a poor or absent response to growth hormone (rhGH) therapy. Mutations in the insulin-like growth factor 1 receptor (IGF1R) gene are associated with impaired growth, intrauterine growth restriction (IUGR), low birth weight and/or length, and postnatal SS. Case Description: A 9-year-old boy, born SGA for birth length, was evaluated for severe SS. Common causes of SS were excluded. At 9 years and 7 months of age, his height was 112.6 cm (−3.99 SDS), weight 18 kg (−3.79 SDS), and BMI 14.2 kg/m² (−1.8 SDS); pubertal development was Tanner stage 1. The target height was 158 cm (−2.62 SDS). Bone age was delayed by approximately one year compared with chronological age. Serum IGF-1 levels were within the upper-normal range for age. GH therapy (0.035 mg/kg/day) was initiated due to the lack of catch-up growth in an SGA subject. After three years of treatment, the height gain was only 0.5 SDS. IGF-1 levels showed a transient treatment-related increase, followed by persistent normalization during ongoing therapy. Next-generation sequencing (NGS) analysis identified novel heterozygous paternal nonsense variant in the IGF1R gene: c.3498C>G (p.Tyr1166Ter). At 12 years of age, impaired fasting glucose and reduced glucose tolerance were detected; consequently, it was decided to discontinue rhGH therapy, also in light of the IGF1R mutation and the lack of height recovery. Conclusions: This case underlines the critical role of genetic testing in the evaluation of patients born SGA. The coexistence of SGA status and an IGF1R gene mutation may provide a clear explanation for both the poor response to rhGH therapy and the increased risk of alterations in glucose metabolism. An extensive narrative review of the literature on growth outcomes and glucose metabolism abnormalities during GH treatment in SGA patients carrying IGF1R variants was also performed. Full article

One of the common issues in the R&D of new drugs is the failure of clinical trials caused by the species-specific inadequacy of animal models to assess drugs’ efficiency and safety. Therefore, systems like organ-on-a-chip and, particularly, liver-on-a-chip (LOC) can be an efficient tool for recapitulating in vivo-like human physiology at the microscale. This review focuses on discussing LOC design, emphasizing its architecture and validation to reveal the trends in searching for a balance between biomimetics and functionality. We found that the huge variety of already published models can be divided into five groups based on their configuration complexity: flat one-channel, flat two-channel, vertically stacked multilayered, hexagonal-patterned, and multi-well chips. While researchers attempt to recapitulate the liver’s histology and its functions in detail by increasing the complexity of devices’ architectonics, industrial companies prefer to promote more simple and flexible solutions. Thus, the LOC designs of the future require neglecting some liver characteristics to make them standardizable and sustainable, which could facilitate their introduction into the market and clinics. Full article

Background: Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure with preserved ejection fraction, resulting from myocardial deposition of misfolded amyloid fibrils derived predominantly from transthyretin (ATTR wild-type [ATTRwt] or variant [ATTRv]) or immunoglobulin light chains (AL). Despite advances in noninvasive imaging and disease-modifying therapies, delayed diagnosis remains common, and clinically actionable molecular biomarkers for early detection, phenotypic discrimination, and therapeutic monitoring are limited. MicroRNAs (miRNAs), small noncoding regulators of post-transcriptional gene expression, have emerged as key modulators of cardiovascular remodeling and systemic amyloid biology. Methods: We performed a comprehensive review of experimental, translational, and clinical studies to evaluate the role of miRNAs in transthyretin and light-chain cardiac amyloidosis, incorporating data from myocardial tissue analyses, circulating miRNA profiling, and mechanistic studies in cellular and animal models. Results: Dysregulated miRNA networks contribute to amyloid-induced cardiac injury by modulating mitochondrial energetics, oxidative stress, inflammation, fibrosis, proteostasis, and neurocardiac signaling. Specific miRNAs, including members of the miR-21, miR-29, and miR-30 families, as well as miR-150-5p and miR-339, have been associated with amyloid burden, adverse myocardial remodeling, plasma cell biology, and disease severity. Distinct circulating and tissue miRNA signatures differentiate transthyretin from light-chain cardiac amyloidosis and correlate with functional status, heart failure biomarkers, and clinical outcomes. Conclusions: MiRNAs represent promising diagnostic and prognostic biomarkers in cardiac amyloidosis and offer mechanistic insights into disease pathogenesis. Integration of miRNA profiling with multimodality imaging and emerging RNA-based therapeutics may enable earlier diagnosis and support precision management of amyloid-related heart failure. Full article

Background/Objectives: Hydrocephalus is defined as the symptomatic accumulation of excessive cerebrospinal fluid (CSF) within the ventricular system. It has an estimated incidence of 85 cases per 100,000 population annually in adults, making it one of the most common conditions managed by neurosurgeons globally. Many conditions may lead to ventricular dilation and hydrocephalus, such as hemorrhage, tumors, infection, trauma, and idiopathic normal-pressure hydrocephalus (iNPH). Regardless of the cause, the gold-standard treatment for hydrocephalus is CSF diversion, usually via a ventriculoperitoneal (VP) shunt. The goal of the present study is to present our experience regarding the etiology of hydrocephalus, management, and shunt failure characteristics over the last 11 years. Methods: A single-center retrospective cohort study was performed. Our cohort consisted of adult patients who were shunted or required revision surgery in our department over the last 11 years. Data regarding the etiology of hydrocephalus, management, shunt characteristics, revision status, and etiology of revision were collected and retrospectively analyzed. Univariable and multivariable logistic regression models were established in order to explore potential associations between the etiology of hydrocephalus and patient characteristics and risk of shunt revision. Revision-free survival probabilities were estimated using the Kaplan–Meier method, while shunt failure rates were also calculated. Results: Our cohort consisted of 114 patients, the median age was 59 (IQR = 26.5) years, and the male-to-female ratio was 1.04:1. The most common cause of hydrocephalus was iNPH (30.7%), followed by post-hemorrhagic (23.7%) and tumor-related hydrocephalus (21.1%). The 12-month revision rate was 13.6%, with overall revision-free survival of 86.4% at one year. Infection (43.2%) was the most common cause of shunt revision, followed by obstruction (16.2%), and mechanical disconnection and migration (18.9%). Younger age was associated with higher risk of revision, while etiology of hydrocephalus and patient sex were not. Conclusions: Our study adds to the pertinent literature data regarding hydrocephalus etiology, management strategies, and shunt failure rates across different hydrocephalus etiologies. Additionally, it serves as a foundation for future studies that could identify predictors of shunt failure, apart from the etiology of hydrocephalus, such as patient characteristics, surgical factors, or shunt types. Finally, we highlight the importance of comprehensive national and potentially continental registries, which will facilitate large-scale analyses. Full article

MicroRNAs (miRNAs) are small non-coding RNAs that play central roles in post-transcriptional gene regulation and cellular homeostasis maintenance. Dysregulation of miRNA expression is increasingly recognized as a key contributor to tissue injury during the acute phase and to disease progression in the chronic phase. Chronic kidney disease (CKD) commonly progresses and ultimately leads to kidney failure through interstitial fibrosis, which is the final common pathway of CKD progression. Interstitial fibrosis is driven not only by fibroblast activation but also by phenotypic transitions in injured tubular epithelial cells, infiltrating macrophages, and peritubular capillary cells. These multifaceted cellular pathways induce and exacerbate interstitial fibrosis, and several miRNAs have been identified as important regulators of these pathways. In addition to fibrotic pathophysiological features, disease-specific dysregulation of miRNAs has been increasingly detected in various causes of CKD, including diabetic kidney disease, chronic glomerulonephritis, and nephrosclerosis. In this review, we provide an integrated overview of miRNA-mediated regulation in CKD, with particular emphasis on cell lineage functions within fibrotic pathways and disease-specific roles. Finally, we discuss the emerging potential of miRNAs as biomarkers and therapeutic targets for CKD and highlight future research directions. Full article

Background: Non-cardiac comorbidities (NCCs) are highly prevalent among patients hospitalized for acute heart failure (HF). However, data from sub-Saharan Africa (SSA) on their distribution across HF phenotypes and association with in-hospital outcomes remain limited. Methods: We prospectively enrolled adults hospitalized with acute HF at a tertiary centre in South Africa between February and November 2023. Ten NCCs were assessed and patients were categorized according to comorbidity burden. The primary outcomes were all-cause in-hospital mortality and length of stay. Multivariable regression and sensitivity analyses were performed to identify predictors of outcomes. Results: Of the 406 patients (mean age 54.9 ± 15.8 years; 51% women), HF with reduced ejection fraction (HFrEF) accounted for 63%, HF with mildly reduced ejection fraction (HFmrEF) for 15%, and HF with preserved ejection fraction (HFpEF) for 21%. The most common NCCs were diabetes (47%), chronic kidney disease (CKD) (46%), obesity (45%), and anaemia (33%). Two-thirds had ≥2 NCCs. The median hospital stay was 8 days (IQR: 5–12) and in-hospital mortality was 3.4% (p > 0.05 across NCC groups). Higher heart rate predicted longer hospitalization, while renin angiotensin system inhibitor (RASi) therapy was associated with shorter stay. Lower Kansas City Cardiomyopathy Questionnaire (KCCQ) score (adjusted odds ratio [aOR] 1.009; 95% confidence interval [CI]: 1.003–1.015) and higher log-transformed NT-proBNP were independently associated with increased in-hospital mortality (aOR 1.85; 95% CI: 1.07–3.50; p = 0.026). Total comorbidity burden was not independently associated with length of stay or in-hospital mortality. Conclusions: Non-cardiac comorbidities are common in acute HF in SSA, and functional status and clinical markers were the strongest predictors of length of stay and in-hospital mortality. Full article

In many densely populated towns and semi-urban areas, masonry buildings often stand close to busy roads, exposing them to blasts from improvised explosives or other localized sources. Such structures are rarely designed to resist sudden explosive forces, making severe damage or even progressive collapse likely. Even moderate-intensity blasts can weaken walls, endanger occupants, and cause significant property loss. Unlike reinforced concrete, masonry is highly susceptible to explosive impact. Therefore, understanding how these buildings behave under blast loads and developing affordable protection methods is crucial. Low-rise unreinforced masonry (URM) structures, usually up to about 13 m in height (roughly 2–4 stories), common in villages, semi-urban regions, and conflict-prone zones, are particularly at risk. In many areas, these poorly constructed buildings lack proper engineering design and are therefore highly vulnerable to blast damage. Non-load-bearing internal dividers and perimeter enclosures are especially prone to lateral displacement, which can initiate instability and, in severe cases, lead to overall structural failure. This research focuses on reducing catastrophic damage in URM walls when exposed to close-proximity blast forces using concrete-based protective coatings, both with and without embedded steel-welded wire mesh. The study references a previously tested laterally supported clay brick wall built with cement–sand mortar as the baseline model, with its behavior validated against experimental findings from existing literature. Two blast cases were considered corresponding to scaled stand-off distances of 2.19 m/kg^1/3 and 1.83 m/kg^1/3, representing moderate flexural-shear cracking and full structural failure, respectively. To replicate the observed behavior, a comprehensive 3D numerical simulation was developed using the ABAQUS/Explicit 2020 solver. The model’s predictions were benchmarked and verified through comparison with reported test data. While both blast intensities were used to confirm computational accuracy, the effectiveness of UHPC and UHPFRC protective coatings with and without embedded wire mesh was specifically evaluated under the more severe collapse scenario (Z = 1.83 m/kg^1/3). Results indicated that at a scaled distance of 1.83 m/kg^1/3, the uncoated URM wall could not withstand the blast because of poor tensile and bending capacity. In contrast, the UHPC- and UHPFRC-coatings provided improved confinement and better stress distribution. When welded wire mesh was embedded, crack control improved further, the interface bond strengthened, and a larger portion of blast energy was absorbed and dissipated. Full article

Background: Members of the virus family Herpesviridae are among the most successful pathogen groups in evolutionary history. They not only pose a serious public health threat to humans but also cause significant economic losses in the global livestock industry. The primary immunological challenge in developing sterilizing vaccines is the lifelong latency of herpesviruses in the nervous system or lymphoid tissues. Methods: This analysis compares the vaccine strategies designed against the five most important Alphaherpesvirinae pathogens: HSV-1/2, PRV, BHV-1, EHV-1/4, and FHV-1. The contrast between the globally licensed veterinary vaccines and the relative stagnation in the field of human HSV vaccines is stark. However, there are notable success stories regarding the implementation of ‘Marker Vaccines’ (DIVA strategies) in veterinary medicine. This review examines various vaccine modalities, assessing their potential to mitigate clinical outbreaks and their shortcomings in preventing viral shedding and establishing latency. Results: This study reveals common technical bottlenecks across species, attributed to immune evasion mechanisms such as the downregulation of MHC I, TAP inhibition, the failure to induce robust mucosal IgA, and safety concerns regarding the recombination of live vectors. Conclusions: This review highlights several promising avenues that could lead to enhanced herpesvirus vaccines and recommends the rational design of T-cell epitopes alongside innovative mucosal adjuvants. Furthermore, it bridges the gap between veterinary and human vaccinology from a One Health perspective, suggesting that lessons learned from veterinary practices could facilitate necessary breakthroughs in human medicine. Full article