Search Results (1,025)

Cefepime-enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination showing good activity against multidrug-resistant (MDR) Gram-negative bacteria producing a variety of β-lactamases. In this systematic review, we aimed to evaluate the available data on resistance to this drug. We performed a thorough search of four databases (Embase, PubMed, Scopus, and Web of Science), as well as backward citation searching, to identify studies containing data on resistance to cefepime-enmetazobactam. The data were extracted and analyzed according to the breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Food and Drug Administration (FDA), or the specific breakpoints reported by the authors of the respective studies. Analysis based on the type of lactamases produced by the isolates was also performed. Ten studies reported in vitro susceptibility testing and mechanisms of antimicrobial resistance. The total number of isolates was 15,408. The activity of cefepime-enmetazobactam against β-lactamase-producing isolates was variable. The resistance of the studied extended-spectrum β-lactamase (ESBL)-producing and ampicillin C β-lactamase (AmpC)-producing isolates was low (0–2.8% and 0%, respectively). The resistance was higher among oxacillinase-48 β-lactamase (OXA-48)-producing and Klebsiella pneumoniae carbapenemase (KPC)-producing isolates (3.4–13.2% and 36.7–57.8%, respectively). High resistance was noted among metallo-β-^lactamase (MBL)-producing isolates (reaching 87.5% in one study), especially those producing New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM), which had the highest rates of resistance. The high activity of cefepime-enmetazobactam against Enterobacterales and selected lactose non-fermenting Gram-negative pathogens, including ESBL-producing and AmpC-producing isolates, makes it a potential carbapenem-sparing agent. The drug should be used after in vitro antimicrobial susceptibility testing in patients with infections caused by OXA-48, KPC, and MBL-producing isolates. Full article

Incineration at sea is a significant source of marine pollution, threatening biodiversity and public health. Although Peru ratified the 1996 London Protocol in 2018, key deficiencies persist in its domestic legal framework, particularly the absence of clear and internationally aligned definitions for “incineration” and “incinerator.” These gaps hinder effective enforcement by the National Maritime Authority (NMA-DICAPI) and limit regulatory compliance with international obligations. This study analyzes Peru’s current legislation in light of the London Protocol and includes a comparative overview of regional regulatory approaches in Latin America. Based on this analysis, the study identifies regulatory inconsistencies that compromise environmental protection and proposes three key legal reforms: (1) refining the definition of “incineration” to reflect international standards; (2) formally incorporating a definition for “incinerator”; and (3) establishing specific administrative and economic sanctions for related infractions. Through comparative analysis with Mexico and Colombia’s approaches, we propose targeted amendments including refined definitions aligned with IMO standards and explicit administrative/economic sanctions. Implementing these recommendations would enhance Peru’s legal clarity, enforcement capacity, and compliance with international maritime law, reinforcing its role as a responsible actor in marine environmental governance. Full article

Fuel price increases have long been a contentious issue in Indonesia, sparking intense public and political debates. This study examines how digital media, particularly Kompas.com and Tempo.co, shape public discourse on fuel price hikes through mediatization. Using discourse network analysis, this study compares the political narratives surrounding fuel price increases during the administrations of Susilo Bambang Yudhoyono (2013) and Joko Widodo (2022). The findings reveal a shift in dominant discourse—opposition to price hikes was prominent in both periods, with government authority and economic justification emphasized in 2013, whereas concerns over rising living costs and social unrest dominated in 2022. This study highlights how mediatization has transformed policymaking from deliberative discussions into fragmented media battles, where digital platforms amplify competing narratives rather than facilitating consensus. Kompas.com predominantly featured counter-discourses, while Tempo.co exhibited stronger pro-government narratives in 2013. This study suggests that while digital media plays a crucial role in shaping policy perceptions, it does not necessarily translate into policy influence. It contributes to the broader understanding of the media’s role in policy debates. It underscores the need for more strategic government communication to manage public expectations and mitigate political unrest surrounding fuel price adjustments. Full article

Aquatic vegetation plays a crucial role in freshwater ecosystems by providing habitats, regulating water quality, and supporting biodiversity. This study aims to monitor and analyze the dynamics of aquatic vegetation in Chimaditida Shallow Lake, Greece, using Sentinel-2 satellite imagery, with validation from field measurements. Data processing was performed using Google Earth Engine and QGIS. The study focuses on discriminating and mapping two classes of aquatic surface conditions: areas covered with Floating and Emergent Aquatic Vegetation and open water, covering all seasons from 1 March 2024, to 28 February 2025. Spectral bands such as B04 (red), B08 (near infrared), B03 (green), and B11 (shortwave infrared) were used, along with indices like the Modified Normalized Difference Water Index and Normalized Difference Vegetation Index. The classification was enhanced using Otsu’s thresholding technique to distinguish accurately between Floating and Emergent Aquatic Vegetation and open water. Seasonal fluctuations were observed, with significant peaks in vegetation growth during the summer and autumn months, including a peak coverage of 2.08 km² on 9 September 2024 and a low of 0.00068 km² on 28 December 2024. These variations correspond to the seasonal growth patterns of Floating and Emergent Aquatic Vegetation, driven by temperature and nutrient availability. The study achieved a high overall classification accuracy of 89.31%, with producer accuracy for Floating and Emergent Aquatic Vegetation at 97.42% and user accuracy at 95.38%. Validation with Unmanned Aerial Vehicle-based aerial surveys showed a strong correlation (R² = 0.88) between satellite-derived and field data, underscoring the reliability of Sentinel-2 for aquatic vegetation monitoring. Findings highlight the potential of satellite-based remote sensing to monitor vegetation health and dynamics, offering valuable insights for the management and conservation of freshwater ecosystems. The results are particularly useful for governmental authorities and natural park administrations, enabling near-real-time monitoring to mitigate the impacts of overgrowth on water quality, biodiversity, and ecosystem services. This methodology provides a cost-effective alternative for long-term environmental monitoring, especially in regions where traditional methods are impractical or costly. Full article

Whilst there has been an increasing trend of women holding academic positions in European Higher Tertiary Institutions (HTIs), leadership positions are held predominantly by men. The study draws on radical feminism theory with which its methodology is aligned by investigating the perceptions of both genders. To that end, the study categorizes the impediments holding women back from breaking the glass ceiling into endogenous and exogenous factors. By doing so, the authors are in a better position to recommend the implementation of policies and procedures to address this inequality and navigate towards achieving sustainable gender equality. The research was conducted using an online survey questionnaire administered among all academic and administrative staff of universities in the Republic of Cyprus, the country with the highest glass ceiling in the EU. The authors found that the binary genders differ in their perceptions of what keeps women from breaking the glass ceiling and that this is attributable to exogenous factors, namely, (a) the walls created by male leaders, reinforcing a feeling of marginalization and mansplaining; and (b) family obligations enhancing women’s experiencing a lack of time and burnout. Furthermore, the exogenous factors and the extremely gendered higher echelons of HTIs underpin the endogenous factor of self-sabotage, making women feel they would rather avoid the toxic leadership environment with its lack of professional credit, a view supported by radical feminism theory. The authors suggest practical policy implications to rectify the gender imbalance in leadership in HTIs and suggest directions for future research. Full article

Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metastatic. In this context, drug repurposing has emerged as a promising strategy to improve treatment options due to the limited number of effective treatments and the heterogeneity of the disease. Indeed, a large number of non-oncology drugs have the potential to address more than one target that could be therapeutic for cancer patients. Although many repurposed drugs are used off-label, efficacy for the new use must be demonstrated in clinical trials. Within regulatory frameworks, both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have procedures to reduce the need for extensive new studies and to expedite the review of drugs for serious conditions when preliminary evidence indicates substantial clinical improvement over available therapy. In spite of several advantages, including reduced development time, lower costs, known safety profiles, and faster regulatory approval, difficulty in obtaining new patents for old drugs with limited protection for intellectual property may reduce commercial returns and disincentivize investments. This review aims to provide comprehensive information on some marketed drugs currently under investigation to be repurposed or used in clinical practice for NETs and to discuss the major clinical challenges. Although drug repurposing is a useful strategy for early access to medicines, the monitoring of the clinical benefit of oncologic drugs during the post-marketing authorization is crucial to support the safety and effectiveness of treatments. Full article

Urban development through property development in central parts of cities rather than through sprawl is key to achieving sustainable future cities. However, realising desired projects in complex city centre environments is challenging and risky due to the involvement of numerous actors. This paper offers novel insights into developers’ perspectives on how the conduct of public authorities influences city centre zoning plan processes. Based on interviews with 11 employees of property development firms, working on mixed-use city centre projects ranging from 1100 to 112,000 m² Gross Floor Area in small and medium-sized Norwegian cities, the study identifies key challenges developers experience in their interactions with public authorities across sectors and administrative levels during planning processes and analyses how these challenges relate to goals, knowledge and power among key actors. The study finds that public authorities can improve the efficiency of zoning plan processes and enhance city centre project delivery by altering their conduct. First, by more explicitly clarifying that the realisation of desired city centre property developments is a primary policy objective, maintaining this focus throughout the processes and taking responsibility for reconciling conflicts in ways that enable feasible projects. Second, by improving their knowledge of the fundamental need for projects to be profitable in order to be realised, and the impact of authorities’ requirements on project viability. Third, by exercising their agenda-setting power more constructively and flexibly throughout the zoning plan process. The paper examines underexplored perspectives in planning research and yields actionable recommendations for planning practice. Full article

This study examines the distinctive male leadership—comprising procurators, parish priests, and chaplains—of the beguinage of St. Elizabeth in Valenciennes during the thirteenth and fourteenth centuries. Contrary to the majority of beguine communities in the southern Low Countries, where leadership appointments were dictated by religious or secular authorities, this community was entitled to elect its male administrators autonomously. The elected were generally influential figures in local religious and secular affairs and maintained a close relationship with the comital family of Hainaut. The analysis will demonstrate how this politically embedded ecclesiastical framework not only ensured doctrinal legitimacy but also mediated conflicts between secular lords and church authorities, thus enabling the community’s survival amid accusations of heresy and institutional repression. By examining the electoral criteria and functional specialization of male leaders, and their interactions with self-governed beguines, this research tries to offer a new perspective on the complex governance strategies of the medieval beguine movement. Full article

Self-realization, a multifaceted concept, has long been a subject of interest in the scientific literature. Given its profound impact on overall well-being and work-related satisfaction, the development of instruments capturing its complexity assumes significant relevance. Therefore, this study presents the development and validation of the META—Measurement for Evolution, Transformation, and Autorealization, a self-report measure designed to assess the propensity for self-realization. The study involved a sample of 634 participants, who completed a survey comprising the META, Satisfaction with Life Scale, Career Adapt-Abilities Scale, General Self-Efficacy Scale, Insight Orientation Scale, and 10-item Connor–Davidson Resilience Scale. The analyses confirmed the statistical solidity of the three hypothesized sections; Part A (Evolutionary Thrust), including Sense of life, Spirit of service, Self-Authorizing, Self-Centering, and Internal Drive for Realization; Part B (Transformative Adaptation), including Propensity for transformation, Distress to change, Adaptability, and Fullness of the Experience; Part C (Work Attitude), including Social Service and Care, Administrative and Office Works, Entrepreneurship, Customer Service and Hospitality, and Manual activities. Factor analyses supported the structural validity of the three hypothesized sections of the META, and all subscales showed good to excellent internal consistency. Significant correlations between the META dimensions/subdimensions and self-realization or well-being outcomes also emerged. The META showed excellent psychometric properties and may be used in various fields, promoting advancements in research and practices supporting well-being and personal fulfilment. Full article

Starting Active Materials for Synthesis (SAMS) represents a critical stage in drug manufacturing, directly influencing the microbiological quality and safety of the final product. The introduction of SAMS marks the point where Good Manufacturing Practices (GMP) begin to apply, which are essential for ensuring sterility and preventing microbial contamination during the synthesis process. However, defining the exact point in the process that qualifies as the SAMS is subject to uncertainties, as earlier stages are not always governed by stringent GMP standards. The regulatory differences between various countries further contribute to this issue. This study explores the implications of SAMS selection and use in relation to sterility and infection control, analyzing the guidelines of major Regulatory Authorities and comparing their approaches to GMP. Regulations from several international regulatory agencies were examined, with a particular focus on microbiological control measures and infection protection in the SAMS manufacturing process. The analysis focused on the microbiological control requirements and safety measures applicable to the stages preceding the introduction of SAMS into the production of the final Active Pharmaceutical Ingredients (APIs). Documents published between 2015 and 2025 were included based on predefined criteria regarding relevance, accessibility, and regulatory authority. The analysis revealed significant discrepancies between regulations regarding the definition and management of SAMS. In particular, the regulations in Mexico and India have notable gaps, failing to provide clear guidelines on SAMS sterility and protection against infectious contamination. Conversely, China has introduced risk-based approaches and early-stage microbiological controls, especially for sterile products, aligning with international standards. The European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), the Pharmaceutical Inspection Co-operation Scheme (PIC/S), and the World Health Organization (WHO) have well-established systems for microbiological quality control of SAMS, including rigorous measures for the validation of suppliers and risk management to ensure that SAMS does not compromise the microbiological safety of the final product. The regulations in Brazil and Canada introduce additional measures to protect the microbiological quality of SAMS, with specifications for contamination control and certification of critical stages. The lack of a harmonized language for the definition of SAMS, coupled with a fragmented regulatory framework, presents a challenge for infection protection in pharmaceutical manufacturing. Key issues include the absence of specific regulations for stages prior to the introduction of SAMS and the lack of standards for inspections related to these stages. A desirable solution would be the mandatory extension of GMPs to the stages before SAMS introduction, with centralized control to ensure sterility and protection against infection throughout the entire manufacturing process. Full article

Neglecting preventive healthcare policies has contributed to the global surge in chronic diseases, increased hospitalizations, declining quality of care, and escalating costs. Non-communicable diseases (NCDs)—notably cardiovascular conditions, diabetes, and cancer—consume over 80% of healthcare expenditure and account for more than 60% of global deaths, which are projected to exceed 75% by 2030. Poor diets, sedentary lifestyles, regulatory loopholes, and underfunded public health initiatives are driving this crisis. Compounding the issue are flawed policies, congressional lobbying, and conflicts of interest that prioritize costly, hospital-based, symptom-driven care over identifying and treating to eliminate root causes and disease prevention. Regulatory agencies are failing to deliver their intended functions. For instance, the U.S. Food and Drug Administration’s (FDA) broad oversight across drugs, devices, food, and supplements has resulted in inefficiencies, reduced transparency, and public safety risks. This broad mandate has allowed the release of unsafe drugs, food additives, and supplements, contributing to the rising childhood diseases, the burden of chronic illness, and over-medicalization. The author proposes separating oversight responsibilities: transferring authority over food, supplements, and OTC products to a new Food and Nutraceutical Agency (FNA), allowing the FDA to be restructured as the Drug and Device Agency (DDA), to refocus on pharmaceuticals and medical devices. While complete reform requires Congressional action, interim policy shifts are urgently needed to improve public health. Broader structural changes—including overhauling the Affordable Care Act, eliminating waste and fraud, redesigning regulatory and insurance systems, and eliminating intermediaries are essential to reducing costs, improving care, and transforming national and global health outcomes. The information provided herein can serve as a White Paper to help reform health agencies and healthcare systems for greater efficiency and lower costs in the USA and globally. Full article

Recently, marketing authorizations were granted by the Federal Drug Administration (FDA) for pegcetacoplan and avacincaptad pegol, which inhibit C3 and C5 complement components, respectively. These two drugs were demonstrated to slow down the growth of atrophic areas in the retina. These authorizations represent a huge breakthrough for patients suffering from geographic atrophy (GA), the late stage of the dry form of Age-related Macular Degeneration (AMD). Until then, no treatment was available to treat this blinding disease. However, these two new compounds inhibiting the complement system are still not available for patients outside of the United States, and they are not devoid of drawbacks, including a poor effect on vision improvement, an increased risk of occurrence of the neovascular form of AMD and the burden of patients receiving recurrent intravitreal injections. Thus, the important medical need posed by GA remains incompletely answered, and new therapeutic options with alternative modes of action are still required. Oxidative stress and inflammation are two major potential targets to limit the progression of atrophic retinal lesions. Dimethyl fumarate, dimethyl itaconate and other activators of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) display antioxidants and immunomodulatory properties that have shown evidence of efficacy in in vitro and in vivo models of dry AMD. Tecfidera^®, whose active principle is dimethyl fumarate, is already commercialized for the treatment of autoimmune diseases such as multiple sclerosis and psoriasis. The aim of this review is to present the rationale and the design of the clinical trial we initiated to test the effectiveness and safety of repurposing Tecfidera^®, which could represent a new therapeutic alternative in patients with the dry form of AMD. Full article

In the United States, the Food and Drug Administration (FDA) is the regulatory authority with the responsibility to evaluate scientific data included in each vaccine’s prescribing information (e.g., safety, indication(s) for use, and dosing schedule) based on several factors, including safety, quality, potency, and effectiveness in preventing disease to assess benefit/risk prior to approval. After approval, the FDA continues to work with sponsors to ensure safety and effectiveness data in the prescribing information remain current. In conjunction with FDA approval or authorization, the Advisory Committee on Immunization Practices (ACIP) recommends immunization dosing schedules and target populations for use. ACIP recommendations that are adopted by the Centers for Disease Control and Prevention (CDC) Director inform national immunization schedules, which influence immunization access, coverage, and provider behavior. This targeted review aims to explore historical instances when vaccine dosing regimens approved by the FDA differ from those recommended by the ACIP, focusing on the frequency and factors behind these differences to inform future ACIP recommendations. Out of n = 78 vaccines assessed, the analysis identified n = 5 vaccines with deviations and only one that reduced dosing. Deviations from the FDA label were determined to be a rare occurrence and are most frequently observed to be additive, not reductive. Full article

Research on the semantic approach to different land use classes is considered an important aspect of overcoming challenges related to proper land management. This research has direct implications for sustainable land management. The aim of this study is to introduce a new land use class in the Polish cadastre based on land use registration systems that function in other European countries. To achieve this, the existing land use registration systems in selected European countries were analyzed. The criterion for including land in the new class will be its actual use. The proposed new land use class may be a highly promising solution for the clear identification of areas with a special functional nature. By proposing the introduction of this new class, authors highlights the areas that, under the current land use registration system, are not clearly identified within the broadly understood categories of built-up and urbanized land. The research findings may also serve as a practical guideline for local authorities responsible for land administration and property taxation. Moreover, accurate land use classification is essential for sustainable land management, as it enables better planning and resource allocation. Improved clarity in land categorization supports environmental protection and balanced development, contributing to long-term sustainability goals. Full article

This paper aims to explore the challenges of maintaining and modernizing legacy systems, particularly COBOL-based platforms, the backbone of many financial and administrative systems. By exploring the DOGE team’s initiative to modernize government IT systems on a relevant case study, the author analyzes the pros and cons of AI and Agile methodologies in addressing the limitations of static and highly resilient legacy architectures. A systematic literature review was conducted to assess the state of the art about legacy system modernization, AI integration, and Agile methodologies. Then, the gray literature was analyzed to provide practical insights into how government agencies can modernize their IT infrastructures while addressing the growing shortage of COBOL experts. Findings suggest that AI may support interoperability, automation, and knowledge abstraction, but also introduce new risks related to cybersecurity, workforce disruption, and knowledge retention. Furthermore, the transition from Waterfall to Agile approaches poses significant epistemological and operational challenges. The results highlight the importance of adopting a hybrid human–AI model and structured governance strategies to ensure sustainable and secure system evolution. This study offers valuable insights for organizations that are facing the challenge of balancing the desire for modernization with the need to ensure their systems remain functional and manage tacit knowledge transfer. Full article