Sustained Reduction Research Articles

Effects of Energy Consumption, GDP and Microfinance on Sustainable Poverty Reduction: Evidence from a Developing Economy

Effects of Energy Consumption, GDP and Microfinance on Sustainable Poverty Reduction: Evidence from a Developing Economy

Fracture mechanism and ductility performances of fiber reinforced shotcrete under flexural loading insights from digital image correlation (DIC)

This paper investigates the fracture mechanism and ductility performance of fiber-reinforced shotcrete (FRS) under flexural loading through digital image correlation (DIC) analysis. The focus is on determining the optimal mix design, utilizing recycled and manufactured fibers in shotcrete through four-point bending tests. These tests reveal significant improvements in flexural strength and ductility, as well as crack resistance, attributed to the synergistic effect of both types of fiber in hybrid fiber reinforcement. Notably, the inclusion of recycled fibers from automobile tires enhances mechanical characteristics and impact resistance, contributing to environmental sustainability and cost reduction. DIC analysis offers crucial insights into crack initiation and propagation in shotcrete, highlighting the impact of fiber reinforcement on crack patterns. Manufactured fibers delay crack onset effectively, while hybridization enhances fracture characteristics, offering improved crack control and flexural strength. The study underscores the potential of hybrid fiber mixes for enhancing structural performance in tunnel support applications, emphasizing the synergistic effect of hybrid of different fiber types. Overall, the research contributes to advancing understanding of fracture behavior in fiber-reinforced shotcrete and provides practical insights for optimizing mix designs to achieve superior mechanical properties and durability.

Development of Ce-doped NH2-UiO-66(Zr) photocatalysts for efficient CO2 reduction in an aqueous system

A series of bimetallic NH2-UiO-66(Zr/Ce) catalysts with varying Zr/Ce molar ratios were synthesized using a straightforward solvothermal method. Among the tested samples, NH2-UiO-66(Zr/Ce1:1) demonstrated superior performance, attributed to its optimized electronic structure, enhanced CO2 adsorption capacity, and efficient separation of photogenerated electron-hole pairs, outperforming the NH2-UiO-66(Zr) variant. The NH2-UiO-66(Zr/Ce1:1) exhibited a bandgap of 2.67 eV, CO2 adsorption capacity of 65.85 cm3/g, and a photocurrent density of 0.43 μA·cm−2. This catalyst achieved achieving a CO production rate of 30.04 μmol·g−1·h−1, representing a 1.66-fold improvement over NH2-UiO-66(Zr), with CO selectivity increasing from 95.2 % to 97.2 %. The results underscore the efficacy of Zr/Ce bimetallic NH2-UiO-66 for CO2 reduction, highlighting the potential of structural modifications in NH2-UiO-66 to enhance photocatalytic performance. This study provides valuable insights into the design and development of advanced catalysts for efficient and sustainable CO2 reduction.

Optimization and Modification of Bacterial Cellulose Membrane from Coconut Juice Residues and Its Application in Carbon Dioxide Removal for Biogas Separation

Driven by environmental and economic considerations, this study explores the viability of utilizing coconut juice residues (CJRs), a byproduct from coconut milk production, as a carbon source for bacterial cellulose (BC) synthesis in the form of a versatile bio-membrane. This work investigates the use of optimization modeling as a tool to find the optimal conditions for BC cultivation in consideration of waste minimization and resource sustainability. Optimization efforts focused on three parameters, including pH (4–6), cultivation temperature (20–30 °C), and time (6–10 days) using Design Expert (DE) V.13. The maximum yield of 9.31% (g/g) was achieved when the cultivation took place at the optimal conditions (pH 6, 30 °C, and 8 days). This approach aligns with circular economy principles, contributing to sustainable resource management and environmental impact reduction. The experimental and predicted optimal conditions from DE V.13 were in good agreement, validating the study’s outcomes. The predictive model gave the correlations of the optimal conditions in response to the highest yield and maximum eco-efficiency. The use of prediction modeling resulted in a useful tool for forecasting and obtaining guidelines that can assist other researchers in calculating optimal conditions for a desired yield. Acetylation of the BC resulted in cellulose acetate (CA) membranes. The CA membrane exhibited the potential to separate CO2 from a CH4/CO2 mixed gas with a CO2 selectivity of 1.315 in a membrane separation. The promising gas separation results could be further explored to be utilized in biogas purification applications.

Magnetic-Manipulation of tribofilm for Si3N4/1045 steel contact toward sustainable reduction in friction and wear

Conventional anti-wear approaches lead to energy inefficiency and excessive waste, posing significant challenges to sustainability and cleaner production. Herein, we investigate the influence of eco-friendly magnetic fields on the tribological behavior of interfaces, with an emphasis on the formation and characteristics of the protective tribofilm. The experimental design combined finite element analysis and friction tests to systematically reveal the relationship between magnetic field strength, oxidation of wear debris, and tribological properties. The results demonstrated that the introduction of a magnetic field led to a 22% reduction in the friction coefficient and a 28% decrease in wear volume. High-intensity magnetic fields refined the wear debris by up to 42.6% and also promoted the oxidation of wear debris, leading to a predominance of Fe3O4 in the tribofilm. The structured arrangement and reorganization of Fe3O4 particles within the tribofilm enhance its density and thickness (from 2 μm to 3 μm). Simultaneously, the rotational motion of Fe2O3 particles at the interface modifies the friction contact state, thereby refining friction performance. The findings underscore the significance of considering magnetic fields in the design of tribological systems for enhanced performance and sustainability.

Globalization and Local Procurement: A Study of Supply Chain Dynamics in Australia and Bangladesh

Purpose: The aim of the study was to analyze the globalization and local procurement: a study of supply chain dynamics in Australia and Bangladesh. Methodology: This study adopted a desk methodology. A desk study research design is commonly known as secondary data collection. This is basically collecting data from existing resources preferably because of its low cost advantage as compared to a field research. Our current study looked into already published studies and reports as the data was easily accessed through online journals and libraries. Findings: The study on strategic sourcing's impact on cost reduction in Australia and Bangladesh manufacturing firms demonstrated significant positive results. It showed that strategic sourcing led to notable reductions in procurement costs, enhanced supplier management, negotiation, and risk mitigation strategies. The findings underscored the importance of aligning procurement strategies with organizational goals for sustainable cost reductions and competitive advantages in the sector. Unique Contribution to Theory, Practice and Policy: Resource dependence theory (RDT), transaction cost economics (TCE) & institutional theory may be used to anchor future studies on analyze the globalization and local procurement: a study of supply chain dynamics in Australia and Bangladesh. Businesses in both Australia and Bangladesh should prioritize building strong relationships with local suppliers to enhance supply chain resilience. Policymakers in both Australia and Bangladesh should create supportive regulatory frameworks that promote local procurement practices.

Remote sensing monitoring of glacier area and volume changes in glacier-fed mountainous watershed on the Northern margin of the Qinghai-Tibet Plateau under climate change.

Steady glacier runoff is related to the security and resilience of water resources in meltwater recharge basins, so the status and change of glaciers and their response to climate change in the upper reaches have received widespread concerns. Here, the spatiotemporal characteristics of glacier wastage in the Upper Reaches of Shule River Basin (URSRB) driven by climate change were analyzed based on multi-source and multi-temporal remotely sensed images. Firstly, we extracted multi-temporal glacier outlines from the Landsat time series data using Google Earth Engine (GEE) for seven different periods every approximately 5years from 1990 to 2020. The spatiotemporal analysis of URSRB glaciers demonstrates a sustained reduction in glacier area from 481.07 ± 24.24 km2 in 1990 to 384.05 ± 22.71 km2 in 2020, corresponding to a glacier shrinkage rate of - 0.67 ± 0.23%/year, characterized by considerable temporal variability. Secondly, multi-temporal DEMs derived from ASTER stereo imagery spanning from 2000 to 2020 were used to compute the glacier surface elevation changes and determine the glacier mass loss. The overall glacier surface elevation change rate was - 0.32 ± 0.14m/year, equivalent to a mass balance of - 0.28 ± 0.12m w.e./year. Lastly, to better apprehend the long-term response of URSRB glaciers to climate change, studies on climate change were carried out based on the EAR5-Land reanalysis dataset. The long-term trend of glacier wastage is attributed to the increase in summer temperature, and the negative effects of increased summer temperature on glaciers exceeded the positive effects of increased annual precipitation. In summary, glaciers in the URSRB have experienced a significant area reduction and accelerated mass loss against the backdrop of climatic warming and humidification.

Research on the Impact of Rural Tourism on Farmer’s Sustainable Livelihood and Coordinated Development (Case Study Jiwodu Village in Yangshuo, Guangxi)

Rural tourism is considered a viable strategy for achieving sustainable rural economic development and poverty reduction, offering significant economic, social, cultural, and ecological benefits. However, as an external force, rural tourism disrupts the livelihood capital and strategies of farmers, significantly influencing their sustainable livelihoods. This paper uses the sustainable livelihood analysis framework from a micro perspective to assess rural tourism's impact on farmers' livelihoods, particularly in Jiwodu Village, Guangxi, China. By categorizing farmers based on the proportion of rural tourism income in their total household income—Tourism-related, Tourism-dominated, and Tourism-exclusive livelihoods—the study constructs a farmer livelihood capital scale, employs a participatory assessment method, and compares changes in the five major livelihood capitals before and after rural tourism development, exploring farmers' perceptions of its impact.

Opportunities and barriers for the integration of Industry 4.0 into small and medium-sized enterprises in Tunisia: analysis with MICMAC and DEMATEL

This study presents a comprehensive framework for understanding the key opportunities and barriers in implementing Industry 4.0 (I4.0) in Tunisian medium-sized enterprises (SMEs), using MICMAC (Matrice d’Impacts Croisés, Multiplication Appliquée à un Classement) and DEMATEL (Decision-Making Trial and Evaluation Laboratory) methodologies, supported by a literature review and expert consultations. Both methods identify crucial opportunities such as digital collaboration and real-time information, along with barriers like under-utilization of academic knowledge and insufficient leadership commitment. While MICMAC emphasizes risk management, not fully recognized by DEMATEL, both converge on similar barriers with nuanced prioritization. Comparing these findings with existing literature highlights commonalities and differences in opportunities and barriers. The study underscores the importance of integrating sustainability and cost reduction into I4.0 frameworks and suggests incorporating technological readiness, leadership support, and innovative business models. For practical implementation, decision-makers should invest in advanced manufacturing technologies, foster collaboration with technology providers, and initiate pilot projects. Enhancing operational agility and efficiency through integrated digital platforms and adaptable systems is essential. Addressing barriers involves securing management support, improving technical expertise, managing resistance to change, and boosting research and development efforts.

Applying palaeoecological analogues to contemporary challenges: community-level effects of canopy gaps caused by systematic decline of a prevalent tree species

Temperate woodland vegetation is initially determined by spatiotemporal and historical factors, mediated by complex biotic interactions. However, catastrophic events such as disease outbreaks (e.g., sweet chestnut blight, ash dieback), infestations of insect pests, and human-accelerated climate change can create canopy gaps due to systematic decline in, or loss of, tree species that was once an important part of the canopy. Resultant cascade effects have the potential to alter the composition of woodland ecosystems quickly and radically, but inherent lag times make primary research into these effects challenging. Here, we explore change in woodland vegetation at 10 sites in response to canopy opening using the Elm Decline, a rapid loss of Ulmus in woodlands across northwestern Europe ~ 5800 years ago that coexisted alongside other stressors such as increasing human activity, as a palaeoecological analogue. For arboreal taxa, community evenness significantly decreased, within-site turnover significantly increased, and richness remained unchanged. Changes in arboreal taxa were highly site-specific but there was a substantial decline in woody climbing taxa, especially Hedera (ivy), across the majority of sites. For shrub taxa, richness significantly increased but evenness and turnover remained consistent. Interestingly, however, there was a significant increase in abundance of shrubs at 70% of sites, including Calluna (heather), Ilex (holly) and Corylus (hazel), suggesting structural change. Surprisingly, there was no change in richness, evenness or turnover for herb taxa, possibly because change was highly variable spatially. However, there was a marked uptick in the disturbance indicator Plantago (plantain). Overall, these findings suggest that woodlands with sustained reduction in, or loss of, a tree species that once formed an important part of the canopy has profound, but often spatially idiosyncratic, impacts on vegetation diversity (richness), composition (evenness), stability (turnover), and on abundance of specific taxa, especially within the shrub layer. Use of this palaeoecological analogue, which was itself complicated by cooccurring changes in human activity, provides a valuable empirical insight into possible cascade effects of similar change in canopy opening in contemporary settings, including Ash Dieback.

Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 30-month analysis of the phase 3 ILLUMINATE-B trial

BackgroundPrimary hyperoxaluria type 1 (PH1) is a genetic disorder resulting in overproduction of hepatic oxalate, potentially leading to recurrent kidney stones, nephrocalcinosis, chronic kidney disease, and kidney failure. Lumasiran, the first RNA interference therapeutic approved for infants and young children, is a liver-directed treatment that reduces hepatic oxalate production. Lumasiran demonstrated sustained efficacy with an acceptable safety profile over 12 months in infants and young children (age <6 years) with PH1 in ILLUMINATE-B (clinicaltrials.gov: NCT03905694), an ongoing, Phase 3, multinational, open-label, single-arm study.MethodsHere, we report interim efficacy and safety findings from ILLUMINATE-B following 30 months of lumasiran treatment. Eligible patients had an estimated glomerular filtration rate (eGFR) >45 ml/min/1.73 m2 if ≥12 months old or normal serum creatinine if <12 months old, and a urinary oxalate to creatinine ratio (UOx:Cr) greater than the upper limit of normal. All 18 patients enrolled in ILLUMINATE-B completed the 6-month primary analysis period, entered an extension period of up to 54 months, and continue to participate in the study.ResultsAt Month 30, mean percent change from baseline in spot UOx:Cr was −76%, and mean percent change in plasma oxalate was −42%. eGFR remained stable through Month 30. In 14 patients (86%) with nephrocalcinosis at baseline, nephrocalcinosis grade improved at Month 24 in 12; no patient worsened. In the 4 patients without baseline nephrocalcinosis, nephrocalcinosis was absent at Month 24. Kidney stone event rates were ≤0.25 per person-year through Month 30. Mild, transient injection site reactions were the most common lumasiran-related adverse events (17% of patients).ConclusionIn infants and young children with PH1, long-term lumasiran treatment resulted in sustained reductions in urinary and plasma oxalate that were sustained for 30 months, with an acceptable safety profile. Kidney function remained stable, low kidney stone event rates were observed through Month 30, and nephrocalcinosis grade improvements were observed through Month 24. Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT03905694.

FP5.9 - Improving the pre-operative administration of medications for patients requiring emergency surgery who are ‘nil-by-mouth’ (NBM)

Abstract The statement ‘nil-by-mouth’ can be misleading with regards to drug administration. Inappropriate pre-operative drug omission or administration can lead to poor patient outcomes, experiences and increased hospital stays. The aim of this quality improvement project was to reduce the number of patients who had regular medications incorrectly administered, omitted or experienced pre-operative medication-related complications. Two interventions were delivered targeted at educating junior doctors and nursing colleagues. Electronic records of general surgical patients requiring emergency surgery in a district general hospital were reviewed. Data on incorrect medication omission, administration and medication-related perioperative complications was retrospectively collected. The percentage of patients who had medications incorrectly administered was 11% pre-intervention, 11% after intervention 1, and 6% after intervention 2. There was a reduction in the number of medications incorrectly omitted from 57% pre-intervention, to 40% after intervention 1 and 0% after intervention 2. One peri-operative medication-linked complication was recorded prior to the interventions which fell to zero cases following both interventions. A sustained reduction in incorrect drug omission and medication-related perioperative complications has been shown following interventions 1 and 2 together, highlighting the importance of involving all members of the multidisciplinary team when aiming to improve how medications are handled preoperatively. No statistically significant change was made to the incorrect administration of medications pre-operatively. This is likely a reflection on the prescribing clinicians within the on-call team who rotate twice weekly. Other interventions targeting a consistent member or process within the on-call team should be explored to ensure follow-through going forward.

Recent Trends and Advancements in Green Synthesis of Biomass-Derived Carbon Dots

The push for sustainability in nanomaterials has catalyzed significant advancements in the green synthesis of carbon dots (CDs) from renewable resources. This review uniquely explores recent innovations, including the integration of hybrid techniques, such as micro-wave-assisted and ultrasonic-assisted hydrothermal methods, as well as photocatalytic synthesis. These combined approaches represent a breakthrough, offering rapid production, precise control over CD properties, and enhanced environmental sustainability. In addition, the review emphasizes the growing use of green solvents and bio-based reducing agents, which further reduce the environmental footprint of CD production. This work also addresses key challenges, such as consistently controlling CD properties—size, shape, and surface characteristics—across different synthesis processes. Advanced characterization techniques and process optimizations are highlighted as essential strategies to overcome these hurdles. Furthermore, this review pioneers the integration of circular economy principles into CD production, proposing novel strategies for sustainable material use and waste reduction. By exploring innovative precursor materials, refining doping and surface engineering techniques, and advocating for comprehensive life cycle assessments, this work sets a new direction for future research. The insights provided here represent a significant contribution to the field, paving the way for more sustainable, efficient, and scalable CD production with diverse applications in optoelectronics, sensing, and environmental remediation.

Chains of misery: surging invasive group A streptococcal disease.

We describe the epidemiology of the recent global surge in invasive group A streptococcal (GAS) disease and consider its proximate and distal causes. We highlight important knowledge gaps regarding clinical management and discuss potential strategies for prevention. Rates of invasive GAS (iGAS) disease were increasing globally prior to the COVID-19 pandemic. Since mid-2022, following the worst years of the pandemic in 2020 and 2021, many countries with systems to monitor GAS syndromes have reported surges in cases of iGAS concurrent with increased scarlet fever, pharyngitis, and viral co-infections. The emergence of the hypervirulent M1UK strain as a cause of iGAS, particularly in high income countries, is concerning. New data are emerging on the transmission dynamics of GAS. GAS remains universally susceptible to penicillin but there are increasing reports of macrolide and lincosamide resistance, particularly in invasive isolates, with uncertain clinical consequences. Intravenous immunoglobulin is used widely for streptococcal toxic shock syndrome and necrotizing soft tissue infections, although there is limited clinical evidence, and none from a completed randomized controlled trial. Intensive and expensive efforts at population-level control of GAS infections and postinfectious autoimmune complications have been only partially successful. The great hope for control of GAS diseases remains vaccine development. However, all modern vaccine candidates remain in the early development stage. In many countries, iGAS rates surged from mid-2022 in the aftermath of pandemic control measures and physical distancing. The emergence of a dominant hypervirulent strain is an important but incomplete explanation for this phenomenon. Clinical management of iGAS remains highly empirical and new data has not emerged. A vaccine remains the most likely means of achieving a sustainable reduction in the burden of iGAS.

Social Inequalities in Colombia: An Analysis from a Cultural and Social Perspective

The objective of this article was to analyze inequalities in Colombia using a strategic prospective approach to identify the social, economic and cultural dynamics that prolong such asymmetries and propose actions to reduce these gaps. The methodology employed is based on the use of advanced prospective analysis tools, such as influence matrices and variable mobility diagrams, in addition to the identification of key actors involved in the formulation and execution of public policies. The results point to the complexity of the interactions between critical variables such as access to technologies, gender equity and youth participation in employment; likewise, the study showed that certain actors, such as the Ministry of Finance and the Ministry of Equality and Equity, have a significant influence on the achievement of objectives that seek to mitigate social inequalities in Colombia. The study concludes the need to work on public policies for social and economic development, but with an approach based on education and changes in cultural patterns in society that allow the gradual reduction of inequalities. The discussion points out that through strategic collaboration among diverse actors and a comprehensive approach, progress can be made towards a sustained reduction of inequalities, promoting a more equitable and inclusive development in Colombian society.

Simulation of Urban Carbon Sequestration Service Flows and the Sustainability of Service Supply and Demand

Simulating ecosystem carbon sequestration service (ECSS) flows is crucial for optimizing the carbon cycle in ecosystems and achieving sustainable balance between the supply and demand of the ECSS. This study integrates least-cost path analysis with Kriging interpolation to simulate the dominant wind direction and corrects the interpolated wind speeds to account for terrain and surface conditions. Carbon emissions are spatially distributed using points of interest and road network data. Ultimately, by traversing the carbon emission rate grids along wind directions, the ECSS flows are simulated. The results reveal that the study area has a small carbon sink area but a high total carbon emission, leading to a situation where the supply of ECSS is insufficient to meet demand. The ECSS flows, based on the simulated wind field, demonstrate high spatial resolution and highlight the service flow corridors with distinct spatial heterogeneity. The study area has a significant carbon surplus, requiring a forest area ten times larger than the study area itself to fully sequester this carbon. These findings provide valuable insights for urban sustainable development and carbon emission reduction strategies.

Enhanced Photocatalytic Properties and Photoinduced Crystallization of TiO2-Fe2O3 Inverse Opals Fabricated by Atomic Layer Deposition.

The use of solar energy for photocatalysis holds great potential for sustainable pollution reduction. Titanium dioxide (TiO2) is a benchmark material, effective under ultraviolet light but limited in visible light utilization, restricting its application in solar-driven photocatalysis. Previous studies have shown that semiconductor heterojunctions and nanostructuring can broaden the TiO2's photocatalytic spectral range. Semiconductor heterojunctions are interfaces formed between two different semiconductor materials that can be engineered. Especially, type II heterojunctions facilitate charge separation, and they can be obtained by combining TiO2 with, for example, iron(III) oxide (Fe2O3). Nanostructuring in the form of 3D inverse opals (IOs) demonstrated increased TiO2 light absorption efficiency of the material, by tailoring light-matter interactions through their photonic crystal structure and specifically their photonic stopband, which can give rise to a slow photon effect. Such effect is hypothesized to enhance the generation of free charges. This work focuses on the above-described effects simultaneously, through the synthesis of TiO2-Fe2O3 IOs via multilayer atomic layer deposition (ALD) and the characterization of their photocatalytic activities. Our results reveal that the complete functionalization of TiO2 IOs with Fe2O3 increases the photocatalytic activity through the slow photon effect and semiconductor heterojunction formation. We systematically explore the influence of Fe2O3 thickness on photocatalytic performance, and a maximum photocatalytic rate constant of 1.38 ± 0.09 h-1 is observed for a 252 nm template TiO2-Fe2O3 bilayer IO consisting of 16 nm TiO2 and 2 nm Fe2O3. Further tailoring the performance by overcoating with additional TiO2 layers enhances photoinduced crystallization and tunes photocatalytic properties. These findings highlight the potential of TiO2-Fe2O3 IOs for efficient water pollutant removal and the importance of precise nanostructuring and heterojunction engineering in advancing photocatalytic technologies.

Prospective REALITI-A Study: 2-Year Real-World Benefits of Mepolizumab in Severe Asthma

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is of proven clinical benefit in severe asthma; prospective, long-term, real-world data in severe asthma are required. Research QuestionThis study aimed to assess the real-world benefit of 2 years’ mepolizumab treatment in severe asthma. Study Design and MethodsREALITI-A was a 2-year, international, prospective study enrolling adults with asthma, newly initiating mepolizumab 100 mg subcutaneously (physician decision). Outcomes in the 1-year pre-mepolizumab versus 2-year follow-up periods included rates of clinically significant asthma exacerbations (CSE; deterioration requiring systemic corticosteroids and/or emergency department [ED] visit/hospitalisation), exacerbations requiring ED visit/hospitalisation, exacerbations requiring hospitalisation, proportion of patients with no exacerbations, median daily maintenance oral corticosteroid (mOCS) dose, proportion of patients discontinuing mOCS completely, asthma control questionnaire (ACQ)-5 score, forced expiratory volume in 1s (FEV1) and adverse events (AEs). ResultsAfter 2 years’ follow-up, 73% of patients (n=599/822) had no record of mepolizumab discontinuation. During the 2-year follow-up versus pre-mepolizumab period (N=822), rates of CSEs, exacerbations requiring ED visit/hospitalisation, or hospitalisation only were reduced by 74%, 79% and 73%, respectively (odds ratio for no CSEs: 10.0; 95% confidence interval: 7.55, 13.25). Median (Q1, Q3) daily mOCS dose decreased from 10.0 (5.0, 14.7) mg at Week 0 (n=297) to 0.0 (0.0, 5.0) mg at Weeks 101–104 (n=168), and the proportion of patients discontinuing mOCS increased progressively to 43% at 1 year and 57% at 2 years. There was a 1.53-point reduction in ACQ-5 scores from baseline at 2 years. At Months 21–24, least square mean FEV1 improved by 142 mL from baseline. Ninety (11%) and 7 (<1%) patients experienced mepolizumab-related AEs and serious AEs during the follow-up period, respectively. InterpretationIn patients with severe asthma, real-world mepolizumab treatment for 2 years was well-tolerated, and was associated with sustained reductions in exacerbations and progressive reductions in mOCS use.

Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy.

Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten. Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion. At the latest data cut-off, 211 (91.3%) of 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0-228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the week 156 and 180 visits, respectively. Sustained reductions from baseline to week 180 occurred in left ventricular outflow tract gradients (mean [standard deviation]: resting, -40.3 [32.7] mmHg; Valsalva, -55.3 [33.7] mmHg), NT-proBNP (median [interquartile range]: -562 [-1162.5, -209] ng/L), and EQ-5D-5L score (mean [standard deviation]: 0.09 [0.17]). Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (week 24) and 63.9% (week 180). At week 180, 74 (77.9%) of 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten). Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up.

The oral ferroportin inhibitor vamifeport prevents liver iron overload in a mouse model of hemochromatosis.

Hemochromatosis is an inherited iron overload condition caused by mutations that reduce the levels of the iron-regulatory hormone hepcidin or its binding to ferroportin. The hepcidin-ferroportin axis is pivotal to iron homeostasis, providing opportunities for therapeutic intervention in iron overload disorders like hemochromatosis. The aim of this study was to evaluate the efficacy of the oral ferroportin inhibitor vamifeport in the Hfe C282Y mouse model, which carries the most common mutation found in patients with hemochromatosis. A single oral dose of vamifeport lowered serum iron levels in Hfe C282Y mice, with delayed onset and shorter duration than observed in wild-type mice. Vamifeport induced transient hypoferremia by inhibiting ferroportin and resulted in a feedback regulation of liver Hamp in wild-type mice, which was absent in Hfe C282Y mice, reflecting the dysregulated systemic iron sensing in this hemochromatosis model. Chronic dosing with vamifeport led to sustained serum and liver iron reductions in Hfe C282Y mice, as well as markedly reducing liver Hamp expression in Hfe C282Y mice, suggesting distinct regulation of liver Hamp expression following acute or continuous iron restriction via vamifeport. At the tested dose, vamifeport retained its activity when combined with phlebotomy and did not significantly interfere with liver iron removal by phlebotomy in Hfe C282Y mice. These data demonstrate that chronic vamifeport treatment significantly reduces serum iron levels and prevents liver iron loading in the Hfe C282Y mouse model of hemochromatosis, thus providing preclinical proof of concept for the efficacy of vamifeport in hemochromatosis with or without phlebotomy.