Failure Conditions Research Articles

A Strain Fitting Strategy to Eliminate the Impact of Measuring Points Failure in Longitudinal Bending Moment Identification

The identification of longitudinal bending moments is a critical component in the health monitoring of ship structures. This study examines the effect of the failure of measurement points on the accuracy of bending moment identification and presents a solution using an XGboost fitting method. The impact of failure point position and quantity on strain fitting accuracy and bending moment identification was investigated by performing a four-point bending experiment in typical failure scenarios. Further numerical analysis was conducted to identify potential sources of errors in the measurement process. Additionally, several XGBoost-based fitting schemes were tested under practical conditions to provide reliable fitting suggestions. The results indicated that the XGboost strain fitting method outperforms conventional methods for removing failed measurement points, resulting in improved accuracy of identification. When the most critical failure condition occurs (i.e., the deck plate measurement points and deck stiffener measurement points fail), the XGboost method can still estimate the strain at the failure points with acceptable accuracy. These results also hold in complex load scenarios. Moreover, in the practical measurement conditions, the arrangement of measuring points includes two sections that are sufficient to support the fitting of failed measurement points by using the XGboost method. The XGboost strain fitting method exhibits promising potential in strain fitting applications.

Simvastatin Attenuates Cardiac Fibrosis under Pathophysiological Conditions of Heart Failure with Preserved Left Ventricular Ejection Fraction by Inhibiting TGF-β Signaling

Introduction: There is still no effective treatment for heart failure with preserved left ventricular ejection fraction (HFpEF), and therapies to improve prognosis are urgently needed. Clinical studies in patients with HFpEF have shown that statins and HMG-CoA reductase inhibitors may reduce their mortality rate. However, the mechanisms underlying the effects of statins on HFpEF remain unknown. In the present study, we examined whether simvastatin administration inhibits the development of cardiac fibrosis in HFpEF model mice. We further examined the contribution of the Smad and mitogen-activated protein (MAP) kinase pathways to the transforming growth factor-β (TGF-β) signaling pathway in the development of HFpEF. Methods: HFpEF animals were prepared by feeding C57BL/6 N mice a high-fat diet and providing water containing N[w]-nitro-l-arginine methyl ester hydrochloride (l-NAME) for 15 weeks. Simvastatin (30 mg/kg/day) or vehicle was administered orally daily during the experimental period. Cardiac function was measured by echocardiography, and cardiac fibrosis was evaluated by Masson’s trichrome staining. Changes in the TGF-β signaling proteins in myocardial tissue were examined by Western blotting. Results: A high-fat diet and l-NAME solution load induced cardiac diastolic dysfunction with cardiac fibrosis. Simvastatin treatment markedly attenuated cardiac fibrosis and reduced cardiac diastolic dysfunction. In addition, simvastatin prevented the increase in phosphorylation levels of Smad (Smad2 and Smad3) and MAPK (c-Raf, Erk1/2) pathway proteins downstream of the TGF-β receptor in cardiac tissue. Conclusions: Our present study demonstrated that simvastatin attenuated diastolic dysfunction by reducing cardiac fibrosis in HFpEF hearts. Furthermore, our findings suggest that the mechanisms by which simvastatin attenuates HFpEF development involve, at least in part, inhibition of the TGF-β signaling pathway, which is activated in the HFpEF heart.

Shared Decision-Making Aids for Pediatric Chronic Hematological and Non-Hematological Conditions: An in-Depth Literature Review

Background: Shared Decision Making (SDM) is a core component of facilitating patient-centered care. When implementing SDM, patients, parents and clinicians make health decisions together, ensuring that families are informed to make decisions based on their values and preferences. This is of particular importance among children and adolescents with chronic conditions, who are often presented with health-related decisions that can have social and psychological implications. Despite increasing recommendations for use of SDM tools, evidence-based recommendations regarding their use in clinical practice are limited. Studies suggest that barriers to SDM implementation include poor quality of information tailored to children and their families, the emotional state of the patients and their families (denial, anxious, overwhelmed, etc.), power imbalance with health care providers, and insufficient time from heavy physicians' workloads. Due to its limited implementation in clinical practice, little is known about proper approaches and outcomes of SDM tools among children and adolescents with chronic conditions. Objectives: To evaluate and summarize the literature related to how SDM tools are being studied and implemented children and adolescents with chronic medical conditions and how they influence decision making and health outcomes. Methods: A literature search was conducted for publications written in English from 2013-2023 using PubMed, MEDLINE, and Google Scholar. Search terms included “shared decision making”, “decision aid,” “pediatrics,” “infant,” “child,” “adolescents,” and “chronic conditions” to ensure adequate representation of the available literature. Relevant articles included those that covering SDM in hematological and non-hematological chronic conditions in pediatrics. Results: Out of 171 studies identified through literature search, 35 were included. Areas in which SDM has been most studied included hematologic and oncologic conditions (n=5), asthma (n=8), autism, other neurodevelopmental disorders (n=6), Obstructive Sleep Apnea (n=4), inflammatory bowel disease (n=1), chronic kidney disease (n=2), and diabetes (n=2), organ failure (n=3), and other conditions (n=4). Of those, 20 studies were descriptive and 15 had an experimental intervention design. Only 4 studies focused on the child's role in SDM while others focused on parent or caregiver role. Implementation of SDM toolkits and patient portals help decrease asthma exacerbations and emergency room visits. Similar toolkits and decision aids developed for decision making in hematologic and respiratory disease have shown reduced decisional conflict regarding treatment choice. In contrast, researched tools developed for diabetes patients did not show improved outcomes but did reduce decisional conflict. Results demonstrate that although patient with greatest functional neurodevelopmental impairment experience less SDM, its use leads to significant improvements in severity of their condition, behavioral, and psychoeducational levels. Research on hematological conditions such as sickle cell, thalassemia, and immune thrombocytopenia all show that their patients are not experiencing SDM, or it's limited to moderate amounts. Both children and parents desire to become more active members of the decision-making progress. Perspective of physicians show that they understand this desire but face barriers such as poor quality of available information, lack of time, or the family's emotional state. Effective training tools are being studied to help enhance SDM care and overcome these obstacles. Conclusions: There is limited evidence for the implementation of pediatric-focused SDM tools in hematological and non-hematological chronic conditions. Published studies in pediatrics have been mostly descriptive and have placed little emphasis on implementation and effectiveness of shared decision-making interventions. Barriers and facilitators to SDM have been explored, but a gap in knowledge still exists regarding the proven methods for SDM. In general, available studies showed benefit in patients' health outcomes, satisfaction with decision making, and treatment adherence. Future research should involve the implementation of patient-centered SDM aids in efforts to overcome known barriers and to establish evidence-based guidelines for their use.

Lymphoid Malignancies in Shwachman-Diamond Syndrome: Incidence, Clinical Features, and Outcomes from the North American SDS Registry

Introduction: Many marrow failure conditions are associated with myeloid malignancy predisposition and a subset carry an increased risk of both myeloid and lymphoid malignancies. The increased risk of myeloid malignancy is known in Shwachman-Diamond syndrome (SDS), however, the risk of lymphoid malignancy in SDS has not been previously reported. Through the North American SDS Registry (SDSR), we identified patients with SDS diagnosed with lymphoma. We report the clinical features and outcomes in these patients as well as the incidence rates of lymphoma, MDS, and AML in this cohort. Methods: Patients with biallelic SBDS mutations enrolled on the SDSR were included for analysis. Age- and sex-specific incidence rates from the SEER Program (2016-2020) were multiplied by person-years of observation to obtain expected numbers of events. The crude rate per 100,000 (100,000*observed number of malignancies/person-years of follow-up) and the standardized incidence ratio (SIR) were calculated. Results: Out of a total of 217 patients with SDS with biallelic SBDS mutations in the SDSR, we identified 3 subjects who developed lymphoma. Case 1: A male patient with biallelic SBDS mutations (c.258 + 2T>C; c.653G>A, p.Arg218Gln) presented with dyspnea and was diagnosed with primary mediastinal B-cell lymphoma at age 16 years. Bone marrow exam was negative for lymphoma but revealed a new del20q clone. He received 6 cycles of R-CHOP. His course was complicated by febrile neutropenia, pleural effusion, deep vein thrombosis, and decreased cardiac ejection fraction requiring subsequent omission of doxorubicin and carvedilol initiation. He is in remission >3 years from diagnosis. Case 2: A male patient with biallelic SBDS mutations (c.258 + 2T>C; c.183_184TA>CT, p.Lys62*) was diagnosed at age 23 years with diffuse large B-cell lymphoma (DLBCL) of the distal stomach and duodenal bulb. Bone marrow exam was negative for malignancy but demonstrated an abnormal karyotype: 46,XY,t(11;16)(q23;q24), del(20)(q11.2q13.3)[9]/46,XY[11]. He received 5 cycles of R-CHOP therapy, which was complicated by febrile neutropenia and S. aureus sepsis. Four years later, he was diagnosed with relapsed DLBCL of the distal ileum and concurrent AML with 5q deletion. He achieved complete remission of both malignancies after 2 cycles of cyclophosphamide, vincristine, prednisone, obinutuzumab, azacitidine, and venetoclax. Therapy was complicated by B. cereus bacteremia with brain abscesses and endocarditis and C. difficile infection. He underwent a matched unrelated donor hematopoietic stem cell transplant and is in remission >180 days from transplant. Case 3: A male patient with biallelic SBDS mutations (c.258 + 2T>C; c.183_184TA>CT, p.Lys62*) was diagnosed with Stage IVB classical Hodgkin lymphoma at age 12 years after presenting with mediastinal syndrome. Bone marrow biopsy was negative for findings suggestive of MDS or malignancy, however, the initial PET-CT was consistent with medullary involvement. He initiated therapy with steroids, doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin and received focal radiation. His course was complicated by recurrent febrile neutropenia, C. difficile colitis, and cellulitis. Due to infectious complications and delayed count recovery after 2 cycles, despite chemotherapy dose reductions, he was transitioned to brentuximab and nivolumab. He demonstrated complete response by Deauville criteria prior to cycle 5 of brentuximab and nivolumab. Among 217 patients with biallelic SBDS mutations in the SDSR, the median age was 12.8 years (range: 0.3 - 52.8). The observed number, rates, and SIR for lymphoma, MDS, and AML are given in Table 1. A high SIR indicates a higher incidence in the SDSR relative to the SEER population in 2016-2020. The observed rate of lymphoma was 28.5 times higher in SDS than the expected rate in the general population. Conclusions: The incidence of lymphoma among patients with SDS is increased relative to the general population but is lower than the incidence of MDS or AML. Increased toxicity with standard therapies was observed in these patients. Given the increased risk of MDS/AML in SDS, which may be further increased by antecedent chemotherapy, non-genotoxic therapies should be investigated for lymphoma in SDS. Our results show that SDS should be added to the list of marrow failure conditions predisposing to both myeloid and lymphoid malignancies.

Absence of Neutropenia in Patient with an Exon 2 Nonsense Mutation in ELANE: Clinical Evidence to Support Gene Therapy Efforts for Severe Congenital Neutropenia

Introduction Severe congenital neutropenia (SCN) is an inherited bone marrow failure condition most often caused by heterozygous mutations in the ELANE gene. While granulocyte colony stimulating factor (G-CSF) is effective in increasing neutrophil counts in the majority of patients, approximately 15% of patients do not respond, necessitating the creation of alternative treatment strategies. Due to its association with significant, life-threatening infections and heightened risk of progression to myelodysplastic syndrome and/or acute myeloid leukemia, SCN has been the focus of recent gene therapy efforts by multiple groups (Nasri et al., 2020; Rao et al., 2021). Pathogenic variants in ELANE most often cause missense mutations or in-frame indels which lead to the production and expression of mutant neutrophil elastase (NE) proteins. Frameshift mutations resulting in out-of-frame stop codons or nonsense mutations are also seen in the third through fifth (final) exons of ELANE due to their ability to circumvent nonsense-mediated decay (NMD) and generate mutant NE. In contrast, frameshift and nonsense mutations in the first and second exons have not been shown to cause neutropenia, most likely because NMD prevents the translation of mutant NE (Rao et al., 2021; Horwitz, 2021). Collectively, these observations suggest that the pathogenicity of ELANE mutations may rely on gain-of-function alterations in mutant NE rather than loss-of-function alterations in normal NE. Because the absence of one copy of ELANE does not appear to be deleterious, one theory posits that therapeutic inactivation of mutant copies of ELANE may have corrective potential (Horwitz et al., 2019; Nasri et al., 2020; Rao et al., 2021). Thus, the focus of several gene editing efforts has been CRISPR/Cas9-mediated knockout in early exons of ELANE in hematopoietic stem and progenitor cells (HSPCs) of patients with ELANE-mutated SCN for allogeneic stem cell transplant (Nasri et al., 2020; Rao et al., 2021). With this study, we sought to understand whether an inherited ELANE mutation analogous to those utilized in gene therapy would cause neutropenia. Case Presentation Here, we present a six-month-old Caucasian male with an ELANE mutation whose clinical findings support this model. The patient was born at full term to a 35-year-old G6P2 mother. The patient's constellation of complex symptoms, including polymicrogyria, corpus callosum dysgenesis, hypotonia, seizures, and feeding difficulties prompted clinical trio whole genome sequencing (WGS) at approximately two months of age. The patient was incidentally found to have a de novo nonsense variant in exon 2 of the ELANE gene (NM_001972.2:c.151G>T, p.[G51*]), predicted to result in protein truncation or NMD. WGS also identified variants of uncertain significance in CHRNB2 and HFE. Importantly, although the ELANE variant was classified as likely pathogenic in the clinical genetics report, the patient has not had clinically significant neutropenia. Absolute neutrophil counts have ranged from 1.27 - 10.95 K cells/μL, with mean and median values of 4.09 and 2.95 K cells/μL, respectively (n=10). The patient has not had a significant infectious history, nor has he required any treatment for hematologic concerns. Discussion The absence of a neutropenia pathology in this patient, at least in his first six months of life, provides evidence in support of gene therapy efforts which seek to ameliorate pathogenic ELANE mutations with gene editing to produce frameshifts in early exons. Most likely, in this patient, NMD of mutant ELANE mRNA prevented its translation, thus allowing for ample production and maturation of neutrophils. A similar pattern was observed in another report which examined patients with whole gene deletions of ELANE (Horwitz et al., 2019), but this is the first report of a nonsense variant analogous to those proposed to be introduced by gene or base editing for gene therapy of SCN. Thus, the present case adds to a growing body of evidence which suggests that ELANE knockout may have therapeutic potential for SCN.

Structural-Missing Tensor Completion for Robust DOA Estimation with Sensor Failure

Array sensor failure poses a serious challenge to robust direction-of-arrival (DOA) estimation in complicated environments. Although existing matrix completion methods can successfully recover the damaged signals of an impaired sensor array, they cannot preserve the multi-way signal characteristics as the dimension of arrays expands. In this paper, we propose a structural-missing tensor completion algorithm for robust DOA estimation with uniform rectangular array (URA), which exhibits a high robustness to non-ideal sensor failure conditions. Specifically, the signals received at the impaired URA are represented as a three-dimensional incomplete tensor, which contains whole fibers or slices of missing elements. Due to this structural-missing pattern, the conventional low-rank tensor completion becomes ineffective. To resolve this issue, a spatio-temporal dimension augmentation method is developed to transform the structural-missing tensor signal into a six-dimensional Hankel tensor with dispersed missing elements. The augmented Hankel tensor can then be completed with a low-rank regularization by solving a Hankel tensor nuclear norm minimization problem. As such, the inverse Hankelization on the completed Hankel tensor recovers the tensor signal of an unimpaired URA. Accordingly, a completed covariance tensor can be derived and decomposed for robust DOA estimation. Simulation results verify the effectiveness of the proposed algorithm.

Development of Various Types of Independent Phase Based Pulsewidth Modulation Techniques for Three-Phase Voltage Source Inverters

Discontinuous pulse-width-modulation (DPWM) methods have been extensively used in the industrial area to reduce overall losses, which decreases the corresponding thermal stress on the power switches of converters. However, local thermal overload can arise due to different aging conditions of semiconductor devices or failure in the cooling system. This leads to reduced reliability of the converter system due to the low expected lifespan of the most aged switches or phase legs. In this paper, the modified DPWM strategies for independent control of per-phase switching loss are introduced to deal with this matter. The proposed per-phase DPWM techniques are generated by modifying the conventional three-phase DPWM methods for reducing the switching loss in a specific leg, whereas the output performance is not degraded. This paper reports on output performance, including output current total harmonic distortion (THD) and power loss of switching devices, analysis for the various modified DPWM strategies for independent control of per-phase switching loss, which is applicable in 2-level 3-phase voltage source inverters (2L3P VSIs). The results are compared to the corresponding continuous PWM technique to verify and analyze the effectiveness and accuracy of the modified DPWM strategies for independent control of per-phase switching loss.

Formula omitted]-Coverage Reliability for Wireless Multihop Network incorporating Boundary Effect

Coverage is one of the crucial performance measures for Wireless Multihop Networks (WMN) and is widely explored by researchers. The coverage performance of the network indicates how effectively the deployed network is able to provide the required coverage for a given period of time. The coverage performance of a finite network is influenced by different factors such as the presence of obstacles in the signal propagation path, the shape and size of the network deployment region, sensor node characteristics, and many others. Therefore, it is necessary to compute the performance of the network before its actual deployment in the desired region. The existing paper proposes an analytical solution for the network coverage considering sensor node failure and boundary effect using three different sensing models i.e., Boolean, Shadow Fading, and Elfes, separately. The Boolean Sensing Model (BSM) is deterministic and ignores the channel randomness, whereas the other two are probabilistic sensing models and are more realistic as they also consider the channel randomness caused by environmental factors. In the existing research, coverage estimation is determined separately for each individual model. However, coverage estimation for all three models and coverage reliability under boundary conditions have not been explored in the literature yet. Coverage reliability is another crucial metric determining how long a network can provide the required coverage. This paper aims to compute the Network Coverage Reliability (NCR) of a WMN deployed in given environments and with sensor node failure conditions. We have proposed an analytical solution to estimate the NCR of a WMN deployed in a finite circular region considering boundary effect using all three models viz., BSM, Shadowing & Multipath Fading (SMF), and Elfes Sensing Model (ESM) assuming sensor node failure condition. The Mean Time to Failure (MTTF) parameter has been determined for all three models and based on that the value of NCR is estimated. The proposed work considers κ-coverage reliability with 1≤κ≤3 where κ is the number of distinct sensor node required to cover the target and render desired NCR for different path fading and non-fading sensing models. The analytical results are validated through simulation runs and found to be consistent. Further, we have analyzed the impact of different parameters, such as the number of sensor node, sensing range, SMF parameters, sensor failure rate, and required reliability on the κ-coverage and κ-coverage reliability, referred to as NCR.

Effectiveness of the Sensitive Nutrition Intervention Program in Accelerating Stunting Reduction in Baubau City

Stunting is a condition of failure to thrive in toddlers due to long-term malnutrition, exposure to repeated infections, and lack of stimulation. Not all short toddlers are stunted, so pediatricians need to differentiate them, but stunted children are scarce. Responding to this problem, the government issued Presidential Regulation (Perpres) Number 72 of 2021 concerning the Acceleration of Reducing Stunting. This regulation is a form of the government's commitment to accelerating the achievement of the stunting reduction target to 14 percent by 2024. This research aims to describe the effectiveness of a sensitive nutrition intervention program to accelerate stunting reduction in Baubau City, focusing on the accuracy of program targets and program outreach. The research used a qualitative design with a phenomenological approach. Data was collected through in-depth interviews with six informants, while secondary data came from related regional government organization (OPD) data. The data was then analyzed in several stages: data collection, reduction, presentation, and conclusion drawing. The research results show that based on indicators of the accuracy of program targets and program outreach in sensitive nutrition intervention programs, the acceleration of stunting reduction in Baubau City has been running effectively even though it has not significantly contributed to reducing the stunting prevalence rate. The decline in the stunting prevalence rate of only 1% shows that the accuracy of program targets still needs to be improved. Access to drinking water and sanitation, community recipients of PKH benefits, and the formation of farming community groups in the future must be several things that need to be maximized to achieve an accelerated reduction in stunting in Baubau City. In conclusion, the consistency of policy implementers must be bound by a shared commitment and shared goals and understanding in efforts to reduce the prevalence of stunting.

Study on the thermal-mechanical coupling characteristics and influencing parameters of heat pipe radiator under accident conditions

Space reactors, due to their strong environmental adaptability, high power output, small size, and long lifespan, are the most important direction for the development of nuclear energy systems in space. The waste heat of the space reactor system needs to be dissipated through a radiative heat exchanger. The current numerical analysis of the heat exchanger predominantly emphasizes heat transfer phenomena while neglecting the effect of mechanical properties. This study utilizes a self-developed, highly accurate thermal-mechanical coupling calculation program to conduct a numerical analysis of the heat pipe radiator. The main objective is to acquire a comprehensive understanding of its thermal-mechanical coupling characteristics and evaluate the effects of various accident conditions on the radiator. The results indicate that the heat dissipation power obtained from the thermal-mechanical coupled calculation is 0.42% higher than that obtained from the standalone heat transfer calculation. Single axial heat pipe failure leads to a 9.13% decrease in heat dissipation power for the affected module, while two axial heat pipes failure results in a 21.17% decrease. The ability of the heat pipe radiator to meet the heat dissipation power requirements under different failure conditions indicates its capacity to effectively respond to a wide range of incidents, thereby emphasizing its superior safety level.

Maternal Cardiovascular Morbidity Events Following Preeclampsia: A Retrospective Cohort Study

(Anesth Analg. 2023;136:728–737) It has been shown that cardiovascular disease is related to preeclampsia. It has also been found that preeclampsia can increase the risk of heart failure, maternal mortality, and other cardiovascular conditions. This study aimed to show the relationship between cardiovascular diseases and preeclampsia in patients.

PENINGKATAN PENGETAHUAN KADER STUNTING DI WILAYAH BINAAN PUSKESMAS BRINGIN MELALUI EDUKASI BERBASIS DIGITAL DENGAN METODE BRAINSTORMING DI ERA GLOBALISASI DALAM PENCEGAHAN STUNTING

Stunting is a condition of failure to grow to achieve normal growth due to poor nutritional status in a long period of time. In the preliminary study, there were 5 children under two who were stunted at the Bringin Health Center and it was found that there was a lack of training and knowledge of cadres related to stunting. PkM participants are Stunting Cadres assisted by Bringin Community Health Center. The purpose of this PkM activity is to increase the knowledge of stunting cadres through digital-based education with the brainstorming method in stunting prevention. This is the basis for conducting community service with the title "Increasing Knowledge of Stunting Cadres in the Assisted Areas of Bringin Health Center through Digital-Based Education With Brainstorming Methods in the Era of Globalization in Stunting Prevention". The activity stage was preceded by coordination and communication activities with the Head of the Puskesmas and the Head of Cadres of the Assisted Areas of the Bringin Public Health Center, Semarang Regency. The implementation of Community Service (PKM) is carried out offline through digital-based education using the brainstorming method. The outputs of this PkM activity are the publication of scientific articles in the PkM journal, a 5-minute video of PkM activities, and the integration of the results of PkM activities in courses. The output of this PkM is expected to have an impact on increasing knowledge, improving the quality of abilities, as well as the real practice of stunting cadres in the Bringin Community Health Center target area in stunting prevention.

Automatic segmentation framework of X-Ray tomography data for multi-phase rock using Swin Transformer approach

A thorough understanding of the impact of the 3D meso-structure on damage and failure patterns is essential for revealing the failure conditions of composite rock materials such as coal, concrete, marble, and others. This paper presents a 3D XCT dataset of coal rock with 1372 slices (each slice contains 1720 × 1771 pixels in x × y direction). The 3D XCT datasets were obtained by MicroXMT-400 using the 225/320kv Nikon Metris custom bay. The raw datasets were processed by an automatic semantic segmentation method based on the Swin Transformer (Swin-T) architecture, which aims to overcome the issue of large errors and low efficiency for traditional methods. The hybrid loss function proposed can also effectively mitigate the influence of large volume features in the training process by incorporating modulation terms into the cross entropy loss, thereby enhancing the accuracy of segmentation for small volume features. This dataset will be available to the related researchers for further finite element analysis or microstructural statistical analysis, involving complex physical and mechanical behaviors at different scales.

Joint Reconfiguration after Failure for Performing Emblematic Gestures in Humanoid Receptionist Robot.

This study proposed a strategy for a quick fault recovery response when an actuator failure problem occurred while a humanoid robot with 7-DOF anthropomorphic arms was performing a task with upper body motion. The objective of this study was to develop an algorithm for joint reconfiguration of the receptionist robot called Namo so that the robot can still perform a set of emblematic gestures if an actuator fails or is damaged. We proposed a gesture similarity measurement to be used as an objective function and used bio-inspired artificial intelligence methods, including a genetic algorithm, a bacteria foraging optimization algorithm, and an artificial bee colony, to determine good solutions for joint reconfiguration. When an actuator fails, the failed joint will be locked at the average angle calculated from all emblematic gestures. We used grid search to determine suitable parameter sets for each method before making a comparison of their performance. The results showed that bio-inspired artificial intelligence methods could successfully suggest reconfigured gestures after joint motor failure within 1 s. After 100 repetitions, BFOA and ABC returned the best-reconfigured gestures; there was no statistical difference. However, ABC yielded more reliable reconfigured gestures; there was significantly less interquartile range among the results than BFOA. The joint reconfiguration method was demonstrated for all possible joint failure conditions. The results showed that the proposed method could determine good reconfigured gestures under given time constraints; hence, it could be used for joint failure recovery in real applications.

Aircraft trajectory prediction and aviation safety in ADS-B failure conditions based on neural network

With the rapid expansion of transportation demand, the number of global flights has rapidly increased, which also poses challenges to air traffic management (ATM). Considering that the radar system in ATM can no longer meet the requirements of flight safety, a very promising next-generation air traffic control technology—Automatic Dependent Surveillance Broadcast (ADS-B) technology has been introduced. However, in the event of on-board equipment failure and local area signal interference, the ADS-B’s signal will disappear or be interrupted. This sudden situation can pose a danger to aviation safety. To solve this problem, this article proposes a bidirectional long short-term memory (Bi-LSTM) network prediction method combining historical ADS-B data to short-term predict the trajectory of aircraft, which can improve aviation safety in busy airspace. Firstly, the problem of frequent dynamic modeling of different types of aircraft was solved by utilizing historical ADS-B data as the data source. Secondly, the data cleansing method is proposed for ADS-B raw data. Furthermore, considering that the spatial trajectory of the aircraft is a complex time series with continuity and interactivity, a bidirectional LSTM based aircraft trajectory prediction framework is proposed to further improve prediction accuracy. Finally, a trajectory with frequent changes was selected for prediction, and compared with 7 prediction methods. The results showed that the proposed method had high prediction accuracy, thus also improving the aviation safety of the aircraft.

Prognostic impact of improvement in quality of life after discharge in patients with ADHF with preserved ejection fraction regardless of the course of HF -PURSUIT-HFpEF registry

Abstract Background Lower quality of life (QOL) is associated with poor clinical outcome in patients with heart failure (HF). However, there is not fully clarified whether the changes in QOL could have prognostic value in patients with HF with preserved ejection fraction (HFpEF). Purpose The purpose of this study is to investigate the prognostic impact of changes in QOL in patients with HFpEF in relation to the changes in condition of heart failure. Methods We prospectively studied 435 patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF) without the poor outcome within 1 year after the discharge. The patients’ QOL was evaluated at discharge and 1 year after the discharge using EuroQol 5 dimensions 5-level (EQ-5D-5L) and the difference in the EQ-5D-5L index at these two time points was used to assess the change in QOL. The primary outcome was all-cause death. Results The median EQ-5D-5L index were 0.753 (0.562-0.875) at discharge and 0.784 (0.646-0.895) at 1 year after the discharge. During a mean follow-up period of 1.6±1.2 years, primary outcome occurred in 92 patients. Patients with improved QOL (defined as equal to or greater than the EQ-5D-5L index at discharge) were significantly younger, had lower volume load on echocardiography and higher level of hemoglobin and serum sodium than those without improved QOL. Both the improved QOL and the improvement of HF (defined as more than -0.035 in the difference in Log NTproBNP value within 1 year after discharge by ROC analysis: AUC 0.570 [0.506-0.635]) were associated with primary outcome at univariate Cox proportional hazard analysis and the improved QOL was significantly independently associated with primary outcome after multivariable adjustment. Kaplan-Meier analysis revealed that patients with improved QOL had significantly lower risk for primary outcome than those without improved QOL not only in the whole study patients (14% vs 27%, p=0.0007) but also both in the group with improving HF (11% vs 22% p=0.0129) and in those with worsening HF (17% vs 31% p=0.0468). Conclusion(s) The improvement in QOL had the prognostic impact in patients with ADHF-HFpEF regardless of the course of heart failure.

Survival analysis of tafamidis use in patients with ATTR cardiac amyloidosis

Abstract Introduction Transthyretin cardiac amyloidosis (ATTR-CM) is a condition in which amyloid fibrils are deposited within the myocardium causing a restrictive cardiomyopathy & resulting heart failure condition. With increasing recognition, a challenge posed, surrounds decisions on optimal treatment strategies. For patients with predominant cardiac amyloidosis, without peripheral/autonomic nervous system involvement, targeted treatments are limited, although the medication tafamidis – a TTR stabiliser, is available since approval by the FDA in 2019 & the European commission in 2020. Aim This study aims to analyse the real-world benefit of tafamidis use in patients with ATTR-CM attending the National Amyloidosis Centre (NAC), UK with regards overall survival from diagnosis when compared to those not on targeted treatment. Methods This was a retrospective study using data taken from a database at the NAC, as all patients included attend the NAC, UK. Patients on tafamidis were matched to control patients (not on targeted treatment) for age, ATTR NAC stage at diagnosis and type of ATTR (i.e. variant or wild-type). Outcome and survival analysis were determined using cox regression analysis and Kaplan-Meier curve using SPSS (V9.0). Results The demographics of patients in both groups are detailed in figure 1. There were 75 patients in both the treatment & control groups. The median follow-up time from diagnosis to data acquisition in the control group was 3.7 years [IQR1.8-5.8] compared to 4.3 years [IQR 3.6-5.4] in the treatment group (p = 0.03). Of note the median duration from diagnosis to starting tafamidis was 2.1 years [1.2-3.2]. Using cox regression analysis, tafamidis use was predictive of a reduced likelihood of death (R = -1.4, p<0.001) [OR 0.24 95%CI 0.12-0.47]. Increasing NAC stage at diagnosis (R = 0.42, P = 0.03), [OR1.5, 95%CI 1.04-2.22] was predictive of increased likelihood of death. Increasing age (R = 0.03, p = 0.07) [OR 1.03, 95%CI 0.98-1.07] was non-significantly associated with increased likelihood of death. There was similarly a significant increase in mortality within the control/non-treatment group of patients (P<0.001) which was reflected in the Kaplan-Meier survival curve (p<0.001). Conclusions In this retrospective analysis, tafamidis use in 75 patients with ATTR-CM, initiated after a median of 2.2 year [IQR1.2-3.2] following diagnosis, was associated with significantly reduced mortality when compared to an untreated matched control group. Survival from diagnosis was similarly improved in the tafamidis group as depicted by the Kaplan-Meier curve. This real-world data suggests support for the use of tafamidis in treating those with ATTR-CM.

Importance of hospital and clinical factors in predicting of 30-day mortality in Takotsubo syndrome: data from the Swedish Coronary Angiography and Angioplasty Registry

Abstract Background Takotsubo syndrome (TS) is an acute heart failure condition that presents with symptoms similar to acute myocardial infarction. TS is often triggered by emotional or physical stress and is an important cause of morbidity and mortality but predictors of mortality in TS patients are not well understood. There is a need to identify high-risk patients and tailor treatment accordingly. Purpose The purpose of this study was to assess the importance of various clinical factors in predicting 30-day mortality in TS patients using a machine-learning algorithm capable of identifying complex relationships between variables. Methods We analyzed data from the nationwide Swedish Coronary Angiography and Angioplasty Registry for all TS patients between 2015-2022. Gradient boosting was used to assess the relative importance of variables in predicting 30-day mortality in TS patients. Results Of the 3,180 hospitalized TS patients, 76% were women. The average age was 68.3 ± 11.2 years. The crude all-cause mortality rate was 2.57% at 30 days. The most important variable in predicting 30-day mortality was the hospital where the patient was treated, with a relative importance of 35.5%. This was followed by the clinical presentation for angiography (21.1%), creatinine level (11.9%), Killip class (8.9%), and age at angioplasty (6.5%). Other less important factors included weight, height, and certain medical conditions such as hyperlipidemia, smoking status, and hypertension. Gender and previous stroke history had a low impact on 30-day mortality in TS patients. Conclusions The treating hospital was the most important factor in predicting 30-day mortality in TS. Since the level of evidence for recommended treatments of TS is low, our findings highlight the importance of conducting randomized studies in this patient group to improve care.

Abstract 15259: The Novel Antisense Oligonucleotide CDR132L Improves Cardiac Function in Heart Failure Across Different Species

Introduction: The chronic progressive condition of heart failure (HF) is, to date, largely irreversible and continues to impose global morbidity. MicroRNAs exert substantial roles in HF progression by orchestrating pathological genes and pathways. Medications directly tackling the roots of the disease are rare, but inhibition of miR-132, a microRNA that was shown to be upregulated upon cardiac remodeling and HF, is a promising approach. Thus, CDR132L, a clinical-stage synthetic antisense oligonucleotide miR-132 inhibitor, can be an innovative therapy for patients with HF. Hypothesis: To examine the effect of CDR132L, different studies were conducted, including in mice and pigs and in a first-inhuman phase 1b safety and tolerability study that revealed preclinical and exploratory efficacy data. Results: MiR-132 transgenic mice developed reduced left-ventricular ejection fraction (LVEF) and cardiac dilatation. CDR132L treatment significantly improved LVEF and reversed cardiac dilatation. The results were confirmed in a porcine transverse aortic constriction model, where the LVEF was significantly improved in the CDR132L treatment group compared to control animals (48.9% vs. 36.1%). In post-MI HF pigs subjected to different treatment and dosing regimens, resulted in a significant and dose-dependent improvement of the cardiac function, illustrated by an up to 10.4% improvement in LVEF to the placebo group at day 56. During a monthly treatment, 87.5% of the animals treated 5x 5 mg/kg with CDR132L showed a ΔLVEF of >7% compared to the placebo group. Additionally, CDR132L improved contractility and the diastolic function by reducing cardiac stiffness. A successful translation of these preclinical results into humans was performed in a CDR132L safety and tolerability Phase 1b clinical trial in HF patients. In an exploratory analysis, the combined endpoint, consisting of patients with a decrease in NT-proBNP levels and/or an absolute increase in LVEF, was significantly met by 79% of the patients in the pharmacodynamically active CDR132L group. Conclusion: Pharmacological miR-132 inhibition by CDR132L improved cardiac function in multi-species models of HF, highlighting the therapeutic potential for clinical use in HF patients.

Abstract 18465: Regulation of Collagen Synthesis and Fibrosis Development in Skeletal Muscle by La-Related Protein 6 (LaRP6)

Introduction: Excessive extracellular matrix (ECM) accumulation, especially collagens, impairs muscle function in muscular dystrophies, aging and muscle trauma (fibrosis). We have found increased skeletal muscle fibrosis in congestive heart failure (CHF) conditions, likely contributing to the impaired muscle functions. Hypothesis: We hypothesized that LARP6 (La Ribonucleoprotein Domain Family Member 6), an mRNA binding protein that coordinates efficient translation of Collagen I α chains, regulates collagen synthesis during skeletal muscle fibrosis in CHF conditions. Approach: Skeletal muscle fibrosis was analyzed in two mouse models, angiotensin II (Ang II) infusion and left anterior descending artery (LAD) ligation. Expression and subcellular localization of Collagen I, Larp6 and myogenic markers (myogenin and Myh3) were analyzed by qRT-PCR, western blotting, in situ hybridization (RNAScope) and immunostaining in hindlimb muscles in vivo and primary myoblasts and fibro/adipogenic progenitor (FAP) cells in vitro . Collagen I levels were also analyzed by picrosirius red staining (PSR). These analyses were performed in a newly-generated Larp6 knockout (Larp6 -/- ) mice. Results: In both Ang II and LAD ligation models, Collagen I mRNA and protein levels were increased together with LARP6, suggesting that LARP6 may regulate Collagen I synthesis in these conditions. In cultured myoblasts and FAPs, LARP6 protein was co-localized with Col1a1 mRNA at endoplasmic reticulum (ER). TGF-β treatment increased the LARP6 and Col1a1 mRNA co-localization, associated with increased pro-collagen I protein levels. Although Larp6 deficiency did not alter basal Collagen I levels, Collagen I induction in fibrotic conditions was decreased in Larp6 -/- mice. We found that thick collagen fibers were more significantly decreased compared to intermediate or loosely-packed thin collagen fibers (PSR signal analysis under the polarized microscope). Conclusions: These data suggest that LARP6 regulates Collagen I protein synthesis and its filament assembly likely in ER by binding to Col1a1 mRNA upon fibrosis induction. Suppression of LARP6 may be a therapeutic strategy to prevent pathophysiological fibrosis development in skeletal muscle.