Recent Failures Research Articles

Quantitative Measurement of Tau Aggregation in Genetically Modified Rats with Neurodegeneration.

Animal models of neurodegenerative diseases have helped us to better understand the pathogenesis of neurodegenerative diseases. However, recent failure to translate pre-clinical model studies to the clinic urges us to develop more rigorous and faithful animal models in neurodegenerative diseases. As genetic manipulation of rats becomes much more accessible due to availability of CRISPR-Cas9 and other genomic editing toolboxes, rats have been emerging as a new model system for neurodegenerative diseases. Even though mouse models have been dominant over the last decades, rats may provide advantages over mice. Rats are more genetically and physiologically closer to humans than to mice. Also, certain rat models can represent deposition of tau, which is one of the key pathological features of Alzheimer's diseases and tauopathies. However, there is an unmet need for standardized, rigorous testing in rat models. We adopted two commonly used biochemical and immunofluorescence methods from mice and human postmortem brains to measure tau aggregation. Due to the intrinsic differences between mice and rats, e.g., size of rat brains, certain equipment is required for rat models to study tau pathologies. Along with specific tools, here we describe the detailed methods for rat models of neurodegenerative diseases.

ПЕРЕГОВОРИ ЩОДО УКЛАДЕННЯ УГОДИ ПРО АСОЦІАЦІЮ МІЖ ЄС І МЕРКОСУР (1999–2023

The article analyzes the negotiations on the conclusion of the association agreement between the EU and Mercosur. The stages of negotiations are defined, starting with the prerequisites for the start of this process (signing in 1995 of the Interregional Framework Cooperation Agreement between the EU and Mercosur), the official start of negotiations in 1999, the results of the main bilateral meetings of representatives of both sides, the resumption of the negotiation process in 2010, 2019, and 2023. The influence of the summits of the heads of state of the European Union and Latin America and the Caribbean, domestic and foreign political circumstances on this process is determined. In the course of the study, it was concluded that negotiations on the conclusion of an association agreement between the EU and Mercosur have become a key issue in the development of relations between the two regional integration associations and an important part of the EU’s foreign policy strategy in Latin America. The prospects for further development of the negotiation process were also analyzed in view of the recent failures to complete the signing of the agreement in 2023 and the current situation in both blocs at the beginning of 2024. Positive factors that influenced the attainment of certain milestones in the negotiation process were identified, such as the leadership role of the Iberian states – Spain and Portugal, which advocated negotiations due to their special linguistic, cultural, historical, and business ties with Latin America. Important stimuli included the summits of the countries of Latin America, the Caribbean, and the EU. Despite the lengthy negotiation process, the agreement was not signed due to resistance from the agrarian lobby in the countries of the European Union, the absence of a common EU strategy for Latin America, and domestic political issues in the Mercosur countries.

Impact of specimen preparation on erosion and post-erosion response of gap-graded soils

Internal erosion is a major threat to the safety and operation of water management structures. Recent failures of embankment dams reported in Australia, Canada, and the US are fresh reminders of the importance of this ongoing issue. Suffusion, the focus of this paper, is one of the main modes of internal erosion occurring in internally unstable soils. It initiates internally, continues slowly with no visible signs, and leads to complete failure if not detected early. Despite recent advances in understanding the influence of suffusion on the mechanical behaviour of internally unstable soils through laboratory investigations, the impact of sample preparation techniques on the soil response during erosion and afterwards is yet to be fully undrstood. When it comes to laboratory investigation of remoulded soils, it has been understood that soil specimens prepared by different techniques show different characteristics and soil fabrics. This research studied the influence of sample preparation methods on the erosion of non-plastic fine particles in internally unstable soils and their mechanical consequences. Soil samples with two gradations, on the borderline of stable and unstable and one fully unstable, were prepared using moist-tamping and wet pluviation techniques and were subjected to a two-hour downward seepage. The erosion progress and pre- and post-erosion drained mechanical behaviour of samples were investigated. Tests result showed a difference in the erodibility of fine particles for the sample on the borderline of internal stability prepared by different techniques, but similar mechanical behaviours for both gradations.

Is there still a place for fenofibrate-statin combination therapy?

Although low-density lipoprotein cholesterol (LDL-C) is the main target for the prevention of atherosclerotic cardiovascular disease (ASCVD), hypertriglyceridaemia (HTG), a common condition characterised by elevated blood triglyceride (TG) levels, contributes to residual cardiovascular risk independently of LDL-C levels. Elevated TG levels are a feature of atherogenic dyslipidaemia, which also includes low HDL-C levels and high levels of atherogenic small, dense LDL, together with accumulation of atherogenic remnant particles. Treatment of HTG includes lifestyle interventions, but these are not always sufficient to significantly reduce TG levels in people at high cardiovascular risk. Current guidelines for the treatment of dyslipidaemias recommend the use of statins as the first choice in people with HTG (TG >200 mg/dL) and high CV risk, and consideration of the use of specific TG-lowering drugs, such as fenofibrate, bezafibrate or icosapent ethyl if HTG persists. Fenofibrate acts by activating the peroxisome proliferator receptor alpha (PPARα), a nuclear receptor that plays an important role in lipid and lipoprotein metabolism, glucose homeostasis and inflammation. Several clinical trials have shown that fibrates may reduce the incidence of major cardiovascular events only in patients with high TG levels and low HDL-C levels, a finding that was also observed with fenofibrate in combination with a statin compared to statin therapy alone. The recent failure of the PROMINENT trial with pemafibrate in combination with a statin highlighted the notion that treatment with fibrates provides a clinical benefit only if they lower apoB levels.

Governance policies in sports federations. A comparison according to their size

Recent failures in the administration of sports federations have led individuals, institutions, and researchers in the field of sports to become increasingly concerned with questions of appropriate forms of governance. This paper provides a snapshot of the characteristics of the governance of Catalan sports federations by analysing key issues such as the composition of governing and executive bodies, the conservatism of presidents, participation and democratization in decision-making processes, and accountability orientation. The research was carried out based on content analysis and the operationalization of a questionnaire specific to the purpose of the research. The results point to some particularities, differences, and correlations between the size (and resources) of sports federations and their governance profile. Empirical evidence is presented on the lack of stakeholder participation in decision-making processes and mechanisms for management control and monitoring. Results identified a lack of accountability orientation and levels of transparency. Few organisations reported having created documents such as a governance code, or risk management manuals, and a low percentage of organisations were concerned about making them publicly available. The results support recent calls for good governance in sport by highlighting key areas for improvement. Authors believe that this contribution can serve as a framework for scholars to investigate other contexts.

Multifaceted Strategy Based on Automated Text Messaging After a Recent Heart Failure Admission

Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem. To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization. This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022. Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team. The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed. Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26). An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome. ClinicalTrials.gov Identifier: NCT04062461.

Enhancing the auditor's mindset: a framework for nurturing professional skepticism

PurposeFollowing recent high-profile audit failures, concern has been expressed that auditors are not demonstrating sufficient skepticism when exercising professional judgment. In particular, client assumptions and estimations relating to hypothetical valuations in financial reporting are not being challenged. This paper seeks to address the issue by advancing a decision-making framework aimed at guiding auditors beyond regulatory reductionist thinking towards an enhanced understanding of the cognitive processes which shape professional judgment in forming a reliable audit opinion.Design/methodology/approachDrawing on the normative philosophical and theological teachings of Bernard Lonergan, the authors' decision-making framework embodies reflective thinking and the data of consciousness to highlight the central role played by enquiry in the dynamics of understanding, judgment and decision-making. Such enquiry elicits challenge of the management bias inherent in hypothetical valuations.FindingsAuditing through a Lonerganian lens allows auditors to reflect on their approach to objective decision-making by offering a set of cognitive tools to enhance the enquiry essential for nurturing professional skepticism.Originality/valueThis paper contributes to the literature by developing the somewhat neglected discourse on the cognitive processes essential for professional skepticism and audit judgment. The authors demonstrate how Lonerganian self-appropriation intensifies an awareness of the recursive cognitive activities pertinent to objective judgment and decision-making. This awakened consciousness has the potential not only to change how auditors question evidence to make informed judgments and decisions, but also to normalize the practice of challenge.

Modern methods of construction (MMC) and innovation negativism in the UK public sector

PurposeThe recent failures and insolvencies of organisations related to the modern methods of construction (MMC) have gained increased attention and controversy across the UK construction sector. Such failures are linked to their inability to achieve an economy of scale and drive key clients to accept the MMC as an alternative to traditional methods. This paper aims to unravel whether a phenomenon of “innovation negativism” has manifested and is contributing to public clients' indecision towards broader MMC, whether this is only linked to past negative experiences formed after the Second World War or whether additional contributing reasons exist to influence adoption.Design/methodology/approachThis study focusses on exploring the decision-making of the UK public construction sector; therefore, this paper adopts a qualitative approach, utilising interviews with 14 carefully selected MMC experts, government advisors and public clients. The phenomenological stance adopted herewith enables the authors to make better sense of the perceptions of the interviewees, leading to the conceptualisation of the innovation negativism phenomenon.FindingsThe paper identifies nine themes that may be argued to promote a profound understanding of the MMC negativism influencing public clients' decision-making. The study has found that more than just the previous negative perceptions formulated post Second World War are driving innovation negativism in the UK public sector. Notably, the emerging themes are incomprehension, lacking evidence, communication, relationship history, bad experiences, uncertainty, inadequate experimentation, the business case and localism.Originality/valueThis study is the first construction management research that acts as a fair departure point to conceptualise the reasoning behind innovation negativism in the construction setting. Through mirroring demand's unipolarity for traditional methods, policy and decision-makers can now rely on the conceptualised reasoning to determine practical solutions to overcome clients' indecisions towards MMC.

Analysis of Challenges and Difficulties in Implementing Information Systems Audit: A Narrative Literature Review

Information Systems Audit has a main role in the value of any organization from developing countries such as integrity, reliability, security, and privacy. Many researchers are interested in the topic of information systems audit due to the large number of recent business failures. Some research focuses on the current cases from developing countries so this research will give a comprehensive overview of information systems audit. Research gap in the existing literature raised the following research question: What are the difficulties and challenges experienced by developing countries in terms of Information Systems Auditing? The narrative literature review for information systems research was undertaken in line with the theory approach to systematic review. This research analyzed a number of categories that aligned with the grand theories related to difficulties and challenges in the implementation of the Information Systems Audit. In conclusion, this literature review shows that the countries face various challenges and difficulties regarding Information Systems Audit which consists of legislation and policies, culture, education, and human resources.

G2C4 targeting antisense oligonucleotides potently mitigate TDP-43 dysfunction in human C9orf72 ALS/FTD induced pluripotent stem cell derived neurons.

The G4C2 repeat expansion in the C9orf72 gene is the most common genetic cause of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Many studies suggest that dipeptide repeat proteins produced from this repeat are toxic, yet, the contribution of repeat RNA toxicity is under investigated and even less is known regarding the pathogenicity of antisense repeat RNA. Recently, two clinical trials targeting G4C2 (sense) repeat RNA via antisense oligonucleotide failed despite a robust decrease in sense-encoded dipeptide repeat proteins demonstrating target engagement. Here, in this brief report, we show that G2C4 antisense, but not G4C2 sense, repeat RNA is sufficient to induce TDP-43 dysfunction in induced pluripotent stem cell (iPSC) derived neurons (iPSNs). Unexpectedly, only G2C4, but not G4C2 sense strand targeting, ASOs mitigate deficits in TDP-43 function in authentic C9orf72 ALS/FTD patient iPSNs. Collectively, our data suggest that the G2C4 antisense repeat RNA may be an important therapeutic target and provide insights into a possible explanation for the recent G4C2 ASO clinical trial failure.

Tooth interior fatigue fracture in automotive differential gears

Tooth Interior Fatigue Fracture (TIFF) is an emerging gear failure mode with significant implications for gear lifetime and reliability, particularly in modern mechanical transmissions subjected to higher loads, smaller sizes, and increased Noise, Vibration, and Harshness (NVH) requirements. This paper investigates fatigue cracks initiated within the interior of pinion and/or side gear teeth in transmission differentials, representing a new area of recent failure detection. Conventional modeling has suggested that TIFF cracks originate in the case/core area of gear teeth, primarily seen in idler transmission gears. However, this study challenges this notion by presenting evidence that cracks often form closer to the middle of the tooth at various heights. These findings indicate the need for a deeper understanding of TIFF, as the existing theoretical descriptions may not fully explain the observed behaviors. By focusing on this novel area of failure, the paper highlights the importance of addressing TIFF to improve the reliability and durability of gears in modern mechanical transmissions.

Tempering Financial Reporting Risk through Board Risk Management

Recent corporate governance failures have heightened stakeholder expectations that the board of directors engage in robust oversight of the firm’s risk management processes. This expectation is in line with widely embraced enterprise risk management frameworks, which assert that strong board risk management is a key component of an entity’s risk management process. We use a hand-coded measure of board engagement in risk management from the recent literature to measure the robustness of that oversight for a sample of large, publicly traded U.S. firms and examine the relationship between robust board risk management (board risk management) and firm-wide strategies for mitigating financial reporting risk. While controlling for board composition-related characteristics, we found a positive association between robust board risk management processes and two avenues for mitigating financial reporting risk (i.e., more effective internal control over financial reporting and the selection of industry specialist auditors). Our results indicate that firms with more robust board risk management are associated with fewer actual instances of materially misstated financial statements and less earnings management.

A Data-driven Framework to Reduce Diesel Spillages in Underground Mines

Several methodologies have been developed to manage diesel in open-cast mining due to its high demand and increasing diesel prices. Although the use of diesel-powered equipment in underground mines has increased over the years, effective management thereof has not received the same attention. With the advent of Industry 4.0, data can be utilised more effectively by modern businesses to identify and solve problems in a structured manner. In this study, an underground mine was used as a case study to determine whether a Data, Information, Knowledge, Wisdom (DIKW) method for diesel management could be coupled with the Six Sigma Define, Measure, Analyse, Improve, Control (DMAIC) tool to make more informed decisions and gain new insights to help reduce diesel wastage underground. The new integrated methodology identified diesel spillages and highlighted the biggest contributors to these underground spillages. The Six Sigma DMAIC domain utilised root cause analysis to determine the reason for recent systems failures, followed by the identification of practical solutions to eliminate up to 200 ML (megalitres) of diesel spillage. With this information, the case study mine stands to save over USD 175,000 per annum.

Experimental investigation of in-flow fluidelastic instability for rotated triangular tube bundles subjected to single-phase and two-phase transverse flows

The in-flow fluidelastic instability of tube bundles prompted renewed interest since the recent unanticipated failure of the replacement steam generators at the San Onofre nuclear power station. A literature review on the topic discloses contrasting views, depending on the tube bundle and flow configuration addressed. In a recent paper, the authors reported experiments using square bundles, subjected to single and two-phase flows. No streamwise instability was observed, for the tested bundle configurations and the flow velocity ranges explored. In the present paper, experimental results obtained at CEA-Saclay for a rotated triangular tube bundle are presented, providing new in-flow fluidelastic data for both single-phase and two-phase transverse flows. The bundle consists of 50 tubes, with reduced pitch P/D = 1.44 and tube diameter D = 30 mm. It was subjected to single-phase (air or water) and two-phase air-water (with homogeneous void fraction in the range 40% to 98%) transverse flows. In the upper region of the bundle, several different flexibility configurations were tested, with up to 15 flexible tubes, mounted using anisotropic supports, which allow for in-flow vibrations. Results presented in the paper include in-flow fluidelastic stability data obtained for both single-phase and two-phase transverse flows. A detailed complex modal identification of the bundle under natural turbulence excitation was performed, at several flow velocities, highlighting the modeshapes which are prone to in-flow instability. Moreover, local void fraction and identified flow regimes are also presented. These results are discussed and compared to those obtained by previous authors, for similar tested configurations.

Analysis of Strategic Response on Employee Performance Among NSE Listed Commercial Banks

Globally, the banking business has seen growing rivalry, necessitating the application of important consistent and skilful decisions to boost the survival rate of numerous institutions. The recent failure of some commercial banks demonstrates that strategic responses for boosting employee performance have yet to be implemented. Employee productivity in Kenya's banking sector has also declined significantly over the years. Employees are also stressed, which leads to decreased productivity, increased absenteeism, low levels of engagement, and low retention rates. The main objective of the study was to determine the influence of strategic response on employee performance among NSE listed Commercial Banks in Kenya. The study was guided by the following specific objectives; to establish the effects of market expansion, cost-cutting strategies and strategic leadership on employee performance among NSE listed Commercial Banks in Kenya. The study also investigated the moderating effect of technology adoption on the relationship between strategic response and employee performance among NSE listed Commercial Banks in Kenya. The study followed a descriptive research design approach focusing on commercial banks based in Nairobi. The target population was all the 10 NSE listed commercial banks and the study data was collected using questionnaires for a period of one month. Due to the population being small, the study used a census sampling approach to cover all 10 commercial banks in Kenya. The study used both primary data. Primary data was collected using semi-structured questionnaires containing both open ended and close ended questions. The content analysis method was used to analyse qualitative data. Quantitative data, on the other hand, was analysed using both descriptive and inferential statistics in SPSS in accordance with the research objectives. Correlation and regression analysis were used in inferential statistics to determine the relationship between the research variables. The findings were presented using tables and figures. From the analysis, it was evident that human resource practices such as recruitment of agencies to help in marketing and selling was mostly adopted. The regression analysis confirmed that strategic leadership and cost-cutting strategies are important factors affecting employee performance in the firms and that market expansion strategies may not have a significant impact on employee performance. The study found that technological strategies may not have a significant moderating effect on the relationship between strategic response and employee performance among NSE listed Commercial Banks in Kenya. The study concluded that there is a positive correlation between strategic response and employees’ performance among NSE-listed Kenyan commercial banks. The study also concludes that strategic leadership and cost-cutting strategies are significant factors affecting employee performance in among the firms. Market expansion strategies and technological strategies may not have a significant impact on employee performance in NSE-listed Kenyan commercial banks. The study further recommended that NSE-listed commercial banks in Kenya should focus on fostering a positive work environment and effective leadership to enhance employee performance. The recommended the NSE listed Kenyan Commercial Banks to continue emphasizing and investing in expansion and cost cutting practices. The study suggested that providing leadership training and support to managers and executives can help them become more strategic in their decision-making. Banks should also carefully evaluate their cost-cutting initiatives to ensure that they do not compromise employee morale, job satisfaction, or overall performance Regular evaluation of technological strategies can help identify areas for improvement and potential opportunities to leverage technology for better employee performance.

Hydraulic fracture failure during excavation of a working shaft for subway station: Forensic diagnosis and postfailure rehabilitation

The recent hydraulic fracture failure of basal strata during excavation of one working shaft for tunnelling in the city of Nantong, China caused destructive consequences on the adjacent urban environments. By extensively reviewing the design and construction materials and field monitoring data, forensic diagnoses were carried out first to reveal the failure mechanism of this accident; then, the entire failure evolution scenario was reconstructed. It was revealed that the incident stemmed directly from a through-wall leakage in a confined aquifer, which resulted from a chain reaction of technical defects, covered excavation, rainfall, and complex subsurface conditions. As a result of massive ingress of confined water into the excavation enclosure, the upward artesian pressures underneath the excavation base outweighed the weights of overlying aquitards; then, a hydraulic fracture failure occurred. In addition to the remedial measures adopted right after the failure to halt the groundwater-soil inrush, a comprehensive rehabilitation plan, which included field monitoring, detection of cavities or loosening zones below the ground level and grouting, was implemented in the following two months to prevent further exacerbation or recurrence of leaking. The long-term field data demonstrated the success of the measures and plans adopted after the failure.

The Demand for Internal Auditors following Accounting and Operational Failures

ABSTRACT Using a comprehensive database of U.S. internal auditor job postings, we find that firms are about 10 percent more likely to post an internal auditor job after the revelation of accounting and operational failures. Also, the demand for internal auditors is stronger when a failure is more severe. Among firms posting internal auditor jobs, firms demand higher-quality internal auditors in response to a failure compared with when there has not been a recent failure. We find evidence of internal audit demand spillovers through connected directors, which helps mitigate concerns that the primary results are due to replacing internal auditors that recently left or due to endogenous links between hiring internal auditors and failure revelations. Overall, our evidence suggests that firms demand internal auditors to help ensure high-quality financial reporting and effective operations. JEL Classifications: G34, J23, M41, M42.

Business model and ESG pillars: The impacts on banking default risk

The recent banks' failures have highlighted the importance of improving banking sector supervision, emphasizing the need to adopt a holistic approach to risk assessment based on an evaluation of a bank's business model (BBM) that combines financial (e.g., bank's balance data) and non-financial information (e.g., bank's ESG performance). In this study, we explore the joint effect of BBM and their environmental (ENV), social (SOC), and governance (GOV) pillars performance on banks' riskiness profile. The study uses a sample of 639 EU banks from 2013 to 2022 and applied a random effects model. Our findings suggest wholesale and retail banks could mitigate default risk, enhancing their ENV pillar performance. Differently, investment banks are encouraged to improve their governance best practices and structure to take advantage in terms of riskiness reduction. These results remain consistent after a series of robustness tests, including the 2SLS model and the Arellano coefficient estimation. Our paper offers practical implications for banking supervisory authorities and practitioners, encouraging to adopt a diversified ESG investment strategy according to bank-specific business models.

Detecting the hot hand in amateur bowlers

ABSTRACT The hot hand, often invoked in describing athletic performances, refers to the notion that the probability of success is conditional upon recent success or failure. The present paper describes a method of identifying hot-hand behavior in which data from amateur 10-pin bowlers were fit with a model containing dynamically varying probabilities of success and failure (hot-hand model) and one with fixed probabilities (stable model). Full-season data of 27 out of 40 bowlers were found to be better fit by the hot-hand model. Following success, different bowlers showed increased or decreased probability of success (hot-hand behavior or underperformance, respectively). Analysis of the two halves of each bowler’s data indicated that the extent of hot-hand behavior or underperformance varied across the season. Overall, results suggest that the conditional probabilities that define performance can vary in an individual over time such that anticipation of hot-hand performance can be a reasonable expectation in certain circumstances.

Sex Differences in Heart Failure With Reduced Ejection Fraction in the GALACTIC-HF Trial

BackgroundWomen with heart failure with reduced ejection fraction (HFrEF) receive less guideline-recommended therapy and experience worse quality of life than men. ObjectivesThe authors sought to assess differences in baseline characteristics, outcomes, efficacy, and safety of omecamtiv mecarbil between men and women enrolled in the GALACTIC-HF (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction) study. MethodsIn GALACTIC-HF, patients with symptomatic heart failure with EF of 35% or less, recent heart failure event, and elevated natriuretic peptides were randomized to omecamtiv mecarbil or placebo. The current analysis investigated differences in baseline characteristics, clinical outcomes, and efficacy and safety of omecamtiv mecarbil between men and women. ResultsOf 8,232 patients analyzed, 21.2% were women. Women more likely self-identified as being Black, had worse symptoms (lower Kansas City Cardiomyopathy Questionnaire Total Symptom Score [KCCQ-TSS]), and were less likely to be treated with angiotensin receptor/neprilysin inhibitor and devices at baseline. Compared with men, women had lower rates of the primary endpoint (adjusted HR: 0.80, 95% CI: 0.73-0.88). Sex did not significantly modify omecamtiv mecarbil’s treatment effect (P interaction = 0.68). Women also had 20% less risk of cardiovascular death, heart failure event, and all-cause death. Women participants had lower rates of serious adverse events. ConclusionsWomen participants of the GALACTIC-HF trial had worse quality of life and were less likely to be treated with guideline-based therapies at baseline. Despite KCCQ-TSS being predictive of poor outcomes in this population, women had a 20% lower risk of an HF event or cardiovascular death compared with men. The beneficial effect of omecamtiv mecarbil did not significantly differ by sex. (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329)