Search

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The role of long-term parenteral support in patients with underlying benign conditions who do not have intestinal failure (IF) is contentious, not least since there are clear benefits in utilising the oral or enteral route for nutritional support. Furthermore, the risks of long-term home parenteral nutrition (HPN) are significant, with significant impacts on morbidity and mortality. There has, however, been a recent upsurge of the use of HPN in patients with conditions such as gastro-intestinal neuromuscular disorders, opioid bowel dysfunction, disorders of gut-brain interaction and possibly eating disorders, who do not have IF. As a result, the European Society of Clinical Nutrition and Metabolism (ESPEN), the European Society of Neuro-gastroenterology and Motility (ESNM) and the Rome Foundation for Disorders of Gut Brain Interaction felt that a position statement is required to clarify - and hopefully reduce the potential for harm associated with - the use of long-term parenteral support in patients without IF. Consensus opinion is that HPN should not be prescribed for patients without IF, where the oral and/or enteral route can be utilised. On the rare occasions that PN commencement is required to treat life-threatening malnutrition in conditions such as those listed above, it should only be prescribed for a time-limited period to achieve nutritional safety, while the wider multi-disciplinary team focus on more appropriate biopsychosocial holistic and rehabilitative approaches to manage the patient's primary underlying condition., Competing Interests: Conflict of interest None declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A significant amount of European basic and clinical neuroscience research includes the use of transcranial magnetic stimulation (TMS) and low intensity transcranial electrical stimulation (tES), mainly transcranial direct current stimulation (tDCS). Two recent changes in the EU regulations, the introduction of the Medical Device Regulation (MDR) (2017/745) and the Annex XVI have caused significant problems and confusions in the brain stimulation field. The negative consequences of the MDR for non-invasive brain stimulation (NIBS) have been largely overlooked and until today, have not been consequently addressed by National Competent Authorities, local ethical committees, politicians and by the scientific communities. In addition, a rushed bureaucratic decision led to seemingly wrong classification of NIBS products without an intended medical purpose into the same risk group III as invasive stimulators. Overregulation is detrimental for any research and for future developments, therefore researchers, clinicians, industry, patient representatives and an ethicist were invited to contribute to this document with the aim of starting a constructive dialogue and enacting positive changes in the regulatory environment., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Non-native species are spreading at an unprecedented rate over large spatial scales, with global environmental change and growth in commerce providing novel opportunities for range expansion. Assessing the pattern and rate of spread is key to the development of strategies for safeguarding against future invasions and efficiently managing existing ones. Such assessments often depend on spatial distribution data from online repositories, which can be spatially biased, imprecise, and lacking in quantity. Here, the influence of disparities between occurrence records from online data repositories and what is known of the invasion history from peer-reviewed published literature on non-native species range expansion was evaluated using 6693 records of the Pacific oyster, Magallana gigas (Thunberg, 1793), spanning 56 years of its invasion in Europe. Two measures of spread were calculated: maximum rate of spread (distance from introduction site over time) and accumulated area (spatial expansion). Results suggest that despite discrepancies between online and peer-reviewed data sources, including a paucity of records from the early invasion history in online repositories, the use of either source does not result in significantly different estimates of spread. Our study significantly improves our understanding of the European distribution of M. gigas and suggests that a combination of short- and long-range dispersal drives range expansions. More widely, our approach provides a framework for comparison of online occurrence records and invasion histories as documented in the peer-reviewed literature, allowing critical evaluation of both data sources and improving our understanding of invasion dynamics significantly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

European eel is considered a "critically endangered" species due to its population decline (c.a. 98 %) in all European waters, primarily because human activities. The eel life cycle is very complex as it includes long migrations, and although aquaculture can help in repopulation, at this time artificially raised eel larvae have little survival. Therefore, to reverse this situation, in 2007 the EU adopted the Eel Regulation, starting a series of plans to improve the conservation and the recovery of the eel population, which included a ban on importing and exporting eels in all EU countries. However, an illegal global market and food fraud developed, turning Europe into the source of the international illegal eel trade. This study reports the evaluation of the welfare consequences of the illegal transport of European glass eels using their epithelial mucus, one of the most promising tools for studying endangered fish species. We also aimed to determine the recovery time required in controlled conditions before their release to the Ebro River. The results showed that high metabolite and cortisol levels were observed in mucus. In addition, the defensive capacity against possible bacterial infections was also affected due to the transport conditions as bacterial co-culture with mucus analysis indicated. Regarding the recovery time, we analysed the same parameters as for the initial transport point resulting in a stabilisation of stress parameters and an increased defensive capacity from day 3 to the final release, but the best results were observed after 2 months under optimal conditions. These findings suggest that transport stress is critical for the survival of glass eels, and the stress and defensive capacities analysis suggests the need for a recovery period prior to release. This approach represents a valuable contribution both for species subject to illegal trade and for the conservation of endangered species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Polyvinyl chloride (PVC), a commonly used plastic across Europe, poses a number of risks at various stages of its life cycle. The carcinogenicity of PVC monomer, the need to use high number and volume of problematic additives, the easiness of fragmentation compared to other thermoplastics, the high volume of use in everyday products and the resulting extent to which European population is potentially exposed to both microplastics and chemicals and, finally, continuous problems during waste management, have raised concerns about impacts of PVC on human health and the environment for decades. As far back as in 2000, the European Commission recognized that PVC causes a wide range of serious problems for the environment and human health. More recently, in April 2022, PVC and its additives were included in the European Union's Restrictions Roadmap, and the European Chemicals Agency's investigation ruled that, to limit the use of some additives and to minimize releases of PVC microparticles, regulatory action would be necessary. Additionally, the Global Plastics Treaty discussions emphasise a need to ensure that plastics that remain in the economy are free of hazardous chemicals, including hazardous polymers. In this paper, we reviewed the available data on PVC microplastic, additives, the end of life options of products made of PVC, and how they all are connected. It is crucial to consider this polymer within the broader context of chemical pollution and circular economy, acknowledging that changes in how we manage our resources are necessary to achieve the goal for a truly non-toxic environment in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Lifetime treatment of aortic valve disease is a matter of increasing debate. Although the risks of a second aortic valve intervention are recognized, little attention has been given to the challenges of a third., Objectives: This study delves into the clinical characteristics, indications, and outcomes of patients undergoing 3 aortic valve interventions., Methods: The THIRD (THree aortIc Reinterventions for valve Disease) registry is a retrospective multicenter, international study of patients who underwent a third procedure on the aortic valve, either surgically or transcatheter-based. Patients undergoing 2 aortic procedures during the same hospital admission were excluded. Baseline characteristics, timing, and mode of bioprosthetic failure, sequence of the procedures, and clinical outcomes were adjudicated according to the Valve Academic Research Consortium criteria., Results: A total of 51 patients from 11 centers were enrolled in this study. Median follow-up time was 565 (314-1,560) days. Eighteen patients (35%) underwent surgical aortic valve replacement (SAVR), and 33 of 51 patients (65%) underwent transcatheter aortic valve replacement (TAVR) as the third intervention. Mean age was 69 ± 14 years, 20 of 51 patients (39%) were female. STS score was 5.0% (Q1-Q3: 3.3%-7.0%). In all TAVR cases, the indication for the first intervention was severe aortic stenosis, as was the indication in 31 of 45 (69%) of SAVR cases (33% bicuspid). The most prevalent procedure sequence was SAVR-SAVR-TAVR (19/51, 37%), followed by SAVR-SAVR-SAVR (10/51, 20%) and SAVR-TAVR-TAVR (10/51, 20%). TAVR-TAVR-TAVR was performed in 4 of 51 cases (8%). The primary indications for a third intervention included structural valve deterioration (SVD) (39/51, 76%), non-SVD (8/51, 16%), and endocarditis (2/51, 4%). Excluding patients with a mechanical prosthesis, predictors of SAVR as third intervention included a lower STS score (OR: 0.58; 95% CI: 0.34-0.98; P = 0.04) and the presence of moderate or severe prosthesis-patient mismatch (OR: 44.8; 95% CI: 2.41-122.00; P = 0.01). Thirty-day device success was 85% for TAVR and 94% for SAVR., Conclusions: In the THIRD registry, SVD emerged as the predominant indication for a third aortic valve procedure. The most frequent procedure sequence was SAVR-SAVR-TAVR, whereas TAVR-TAVR-TAVR was less common. Although the short-term outcomes in our selected cohort were favorable, further investigation is needed., Competing Interests: Funding Support and Author Disclosures Dr Tarantini has received honoraria for lectures/consulting from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, GADA. Dr Tang is a physician proctor, consultant, and advisory board member for Medtronic; is a consultant and advisory board member for Abbott Structural Heart; is an advisory board member for Boston Scientific and JenaValve; and has received speaker honoraria from Siemens Healthineers. Dr Kim has received personal fees from Abbott, Boston Scientific, Edwards Lifesciences, HI-D Imaging, Meril Life Sciences, and Shockwave Medical. Dr Pilgrim has received research, travel or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens; and has received speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife. Dr Greenbaum has received institutional research support from Abbott Vascular, Ancora Heart, Edwards Lifesciences, Gore Medical, JenaValve, Medtronic, Polares Medical, Transmural Systems, and 4C Medical; has received consulting fees from Abbott Vascular, Edwards Lifesciences, and Medtronic; and has an equity interest in Transmural Systems. Dr Webb is a consultant for Edwards Lifesciences; and has received research funding from Edwards Lifesciences, Medtronic, and Boston Scientific. Dr Makkar is a consultant for and received research grants from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific. Dr Franco is a proctor for Abbott Vascular and Edwards Lifesciences. Dr De Backer has received institutional research grants and consulting fees from Boston Scientific. Dr Fovino received consulting fees from Edwards Lifesciences and research grant from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous studies have documented ethnic and sociodemographic disparities in exposure to drinking water (DW) contaminants. A majority were conducted in the U.S., with fewer studies conducted in other regions. This research aims to assess available evidence regarding environmental justice (EJ) issues in Europe, identify contaminants and potential drivers. A Scoping Review was conducted, exploring the existing European studies from 1990 to 2022. The review encompasses types of DW contaminants studied in relation to EJ, research designs, and potential drivers contributing to inequalities in exposure to specific contaminants. In addition, a case study was conducted in Ille-et-Vilaine, France, focusing on contaminants identified in the review and using a national monitoring database. Inequalities in contaminants' exposure were assessed using a composite deprivation index, FDep, at the census tract level (IRIS) applied in multilevel models and geographically weighted regression models, accounting for the rural-urban heterogeneity. Results show a limited number of primary studies focusing on EJ and DW contaminants exposure in Europe (n = 16). Various chemical contaminants such as nitrates, trihalomethanes (THMs), heavy metals, fluoride and pesticides have been assessed. Case study findings suggest some association between FDep and contaminants, with a different level of correlation depending on the contaminant. THMs show a negative correlation with deprivation, while lead displays a positive correlation related to the FDep. Disparities in exposure were also found according to the spatial scale of analysis. In rural areas, higher deprivation levels were associated with higher levels of nitrate (OR: 1.47; 95%CI: 1.02, 2.15) and lower level of fluoride (OR: 0.16; 95%CI: 0.07, 0.30) or THMs (OR: 0.73; 95%CI: 0.55, 0.98) in tap water. This study emphasizes the need for comprehensive research on EJ and DW contaminants exposure on a larger scale. Understanding complex interactions between contaminant distribution, socioeconomic factors, and exposure is essential for addressing EJ in drinking water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study unveils the establishment of the United Kingdom-Netherlands Decomposition Experimental Research (UNDER) working group, marking a pioneering initiative in practical Forensic Taphonomy within the UK. Our primary objective was to craft a cohesive multidisciplinary framework, designed to ethically orchestrate, execute, and assess human decomposition. Concurrently, we aimed to amass data through human burials, fostering collaboration among diverse forensic experts across Europe. The compilation of data collected over the year, elucidates the comprehensive utilisation of cadavers through a multifaceted scientific methodology. This paper discusses the triumphs, challenges, and innovative solutions encountered during this undertaking, providing a blueprint for forthcoming European research in Forensic Taphonomy. Our efforts support the comparability of longitudinal studies and give strategies to address the challenges posed by the scarcity and diversity of human donors in forensic science. Moreover, we propose the adoption of a dynamic scientific research management framework, which includes thorough identification, measurement, analysis, and application of solutions. Emphasis is also placed on adeptly managing business processes to ensure sustained relevance in both research and other stakeholders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Fine particulate matter (PM 2.5 ) is a key air quality indicator due to its adverse health impacts. Accurate PM 2.5 assessment requires high-resolution (e.g., atleast 1 km) daily data, yet current methods face challenges in balancing accuracy, coverage, and resolution. Chemical transport models such as those from the Copernicus Atmosphere Monitoring Service (CAMS) offer continuous data but their relatively coarse resolution can introduce uncertainties. Here we present a synergistic Machine Learning (ML)-based approach called S-MESH (Satellite and ML-based Estimation of Surface air quality at High resolution) for estimating daily surface PM 2.5 over Europe at 1 km spatial resolution and demonstrate its performance for the years 2021 and 2022. The approach enhances and downscales the CAMS regional ensemble 24 h PM 2.5 forecast by training a stacked XGBoost model against station observations, effectively integrating satellite-derived data and modeled meteorological variables. Overall, against station observations, S-MESH (mean absolute error (MAE) of 3.54 μg/m 3 ) shows higher accuracy than the CAMS forecast (MAE of 4.18 μg/m 3 ) and is approaching the accuracy of the CAMS regional interim reanalysis (MAE of 3.21 μg/m 3 ), while exhibiting a significantly reduced mean bias (MB of -0.3 μg/m 3 vs. -1.5 μg/m 3 for the reanalysis). At the same time, S-MESH requires substantially less computational resources and processing time. At concentrations >20 μg/m 3 , S-MESH outperforms the reanalysis (MB of -7.3 μg/m 3 and -10.3 μg/m 3 respectively), and reliably captures high pollution events in both space and time. In the eastern study area, where the reanalysis often underestimates, S-MESH better captures high levels of PM 2.5 mostly from residential heating. S-MESH effectively tracks day-to-day variability, with a temporal relative absolute error of 5% (reanalysis 10%). Exhibiting good performance at high pollution events coupled with its high spatial resolution and rapid estimation speed, S-MESH can be highly relevant for air quality assessments where both resolution and timeliness are critical., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The accumulation of nitrogen (N) in moss tissue has proven to be a reliable marker of increasing N deposition. However, this measurement does not offer additional data about the origin of pollution. In this respect, the analysis of the N isotopic ratios might be a helpful tool in providing supplementary information about the nature of the nitrogenous species in biomonitoring surveys. Furthermore, isotopic signatures have been extensively used in the study of N and carbon (C) biogeochemical cycles. The main purpose of this study was to determine N and C elemental contents and their stable isotopes in mosses to investigate atmospheric pollution patterns across Europe. We aimed at identifying the main N polluted areas and evaluating the potential use of isotopic signatures in the attribution of pollution sources at a regional scale. With these objectives in mind, >1300 samples from 15 countries from Europe, all of them participants of the ICP-Vegetation programme 2005-2006, were analyzed for their C and N contents and δ 15 N and δ 13 C. The results were compared to those derived from EMEP model, which provided modeled deposition and emission data, as well as to the predominant land uses at the sampling sites (based on CORINE Land Cover). This evaluation suggests that additional measurements of stable C and N isotopes in mosses could be a valuable tool in European environmental surveys. Such measurements not only provide useful information for identifying probable pollution sources but also enable the quantification of their contributions, serving as biological indicators of significant environmental processes. This study presents the first quantitative assessment of major atmospheric nitrogen (N) sources based on stable isotope analysis on a European scale, establishing a framework for evaluating historical changes in N across the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The European Fans in Training (EuroFIT) program integrated need-supportive motivational strategies from Self-Determination Theory (SDT) in the design of a healthy lifestyle program delivered to overweight or obese male football fans (n = 1113; mean age of 45.9 [SD = 9.0] years old and BMI of 33.2 kg/m2 [SD = 4.6]) in professional football club settings in the UK, Portugal, Norway and the Netherlands. With a critical realist approach, we developed a structured thematic framework analysis based on Self-Determination Theory (SDT) to investigate the process of change in men who participated in the EuroFIT randomized controlled trial (RCT). We examined whether men's experiences of the social context of EuroFIT, and whether their engagement with the program's motivational strategies supported or frustrated their basic psychological needs while attempting to change their lifestyle behaviours. We found that men in all countries perceived the social contexts of the EuroFIT program as mostly needs-supportive, and that they found engagement with most of the program components helpful in supporting their psychological needs when initiating health behaviour changes. However, some of the program elements in the EuroFIT program were perceived as needs-frustrating by some participants and need-supportive by others. Implications for the use of need-supportive motivational strategies in designing future lifestyle interventions in sport settings to promote health behaviour change among male football fans are discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to provide an overview of analytical methods in scientific literature for comparing uncontrolled medicine trials with external controls from individual patient data real-world data (IPD-RWD) and to compare these methods with recommendations made in guidelines from European regulatory and health technology assessment (HTA) organizations and with their evaluations described in assessment reports., Methods: A systematic literature review (until March 1, 2023) in PubMed and Connected Papers was performed to identify analytical methods for comparing uncontrolled trials with external controls from IPD-RWD. These methods were compared descriptively with methods recommended in method guidelines and encountered in assessment reports of the European Medicines Agency (2015-2020) and 4 European HTA organizations (2015-2023)., Results: Thirty-four identified scientific articles described analytical methods for comparing uncontrolled trial data with IPD-RWD-based external controls. The various methods covered controlling for confounding and/or dependent censoring, correction for missing data, and analytical comparative modeling methods. Seven guidelines also focused on research design, RWD quality, and transparency aspects, and 4 of those recommended analytical methods for comparisons with IPD-RWD. The methods discussed in regulatory (n = 15) and HTA (n = 35) assessment reports were often based on aggregate data and lacked transparency owing to the few details provided., Conclusions: Literature and guidelines suggest a methodological approach to comparing uncontrolled trials with external controls from IPD-RWD similar to target trial emulation, using state-of-the-art methods. External controls supporting regulatory and HTA decision making were rarely in line with this approach. Twelve recommendations are proposed to improve the quality and acceptability of these methods., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2025. Published by Elsevier Inc.)

Background: In patients with acute coronary syndromes (ACS) and multivessel coronary disease, immediate complete revascularization was noninferior to staged complete revascularization for the primary composite outcome at 1 year. The authors report clinical outcomes at 2 years of follow-up., Methods: Patients with ACS and multivessel coronary disease were randomly assigned to immediate complete revascularization or to staged complete revascularization at 29 sites in Europe. The primary outcome was the composite of all-cause mortality, myocardial infarction, any unplanned ischemia-driven revascularization, and cerebrovascular event., Results: In total, 764 patients were enrolled and randomly allocated to the immediate complete revascularization arm and 761 to the staged complete revascularization arm. Two-year follow-up was complete for 97.6% of patients. At 2 years, the primary outcome had occurred in 12.5% of patients in the immediate complete revascularization group and 12.4% of patients in the staged complete revascularization group (HR: 0.98; 95% CI: 0.73-1.30; P = 0.88). Myocardial infarction occurred more frequently in the staged complete revascularization group (6.2% vs 3.8%; HR: 0.60; 95% CI: 0.37-0.96; P = 0.032). In the immediate complete revascularization and staged complete revascularization groups, the rates of all-cause mortality (3.3% vs 2.0%; HR: 1.67; 95% CI: 0.88-3.16; P = 0.12), any unplanned ischemia-driven revascularization (7.0% vs 7.9%; HR: 0.87; 95% CI: 0.60-1.26; P = 0.57), and cerebrovascular event (2.5% vs 1.7%; HR: 1.39; 95% CI: 0.68-2.83; P = 0.37) were not significantly different., Conclusions: In patients with ACS and multivessel disease, there was no significant difference between immediate complete revascularization and staged complete revascularization with respect to the composite outcome of all-cause mortality, myocardial infarction, any unplanned ischemia-driven revascularization, and cerebrovascular event at 2 years. Immediate complete revascularization was associated with a significant reduction in myocardial infarction, mainly due to fewer early events. (Direct Complete Versus Staged Complete Revascularization in Patients Presenting With Acute Coronary Syndromes and Multivessel Disease [BioVasc]; NCT03621501)., Competing Interests: Funding Support and Author Disclosures Biotronik provided an unrestricted research grant. Dr Diletti has received institutional research grants from Biotronik, Medtronic, ACIST Medical Systems, and Boston Scientific. Dr den Dekker has received institutional research grants from Biotronik. Dr Van Mieghem has received institutional research grants from Biotronik, Abbott, Medtronic, Edwards Lifesciences, PulseCath, Abiomed, and Daiichi-Sankyo; has received speaker fees from Abiomed and Amgen; and has received a travel grant from JenaValve. Dr Bennett has received institutional grants from Biotronik, Abbott Vascular, and Shockwave Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with refractory angina are often ineligible for revascularization and have poor quality of life despite optimal medical therapy. The coronary sinus (CS) Reducer (Shockwave Medical Inc) was safe and effective in the treatment of refractory angina in the COSIRA (Coronary Sinus Reducer for Treatment of Refractory Angina) randomized sham-controlled trial., Objectives: This study sought to perform the primary endpoint analysis of the complete REDUCER-I (An Observational Study of the Neovasc Reducer System) study cohort., Methods: REDUCER-I is a nonrandomized, "real-world" study of patients with refractory angina treated with the CS Reducer conducted at 25 centers from 9 European countries. The primary effectiveness endpoint was an improvement in Canadian Cardiovascular Society (CCS) class at 6 months. The primary safety endpoints were major adverse cardiac events and device- or procedure-related serious adverse events through 30 days. Study follow-up is planned through 5 years with some interim 3-year analyses included here., Results: From 2016 to 2023, 400 patients were enrolled, including 78.0% (312/400) male patients, 54.3% (216/398) with previous myocardial infarction, 73.6% (293/398) with previous revascularization, and 72.0% (280/389) CCS class III/IV. Major adverse cardiac event and serious adverse event rates were 1.6% (95% CI: 0.7-3.6) and 1.1% (4/371), respectively, with no deaths within 30 days. At 6 months, 69.8% (240/344) of patients improved by ≥1 CCS class. Six-minute walk distances improved by 34.1 ± 85.8 m at 6 months (P < 0.0001). Interim 3-year results showed CCS class and Seattle Angina Questionnaire quality of life improvements were sustained (P < 0.0001)., Conclusions: The complete primary endpoint analysis of the REDUCER-I study shows patients with refractory angina were safely and effectively treated with the CS Reducer. Improvements in angina and quality of life appear sustained through 3 years., Competing Interests: Funding Support and Author Disclosures The REDUCER-I study is sponsored by Shockwave Medical Inc, although no specific funding was provided for this analysis. Dr Verheye serves as a proctor for Shockwave Medical Inc; and has received honoraria from Shockwave Medical Inc. Dr de Silva serves as a proctor for Shockwave Medical Inc; and has received honoraria from Shockwave Medical Inc. Dr West is an employee of Shockwave Medical Inc. Dr Banai has received honoraria from Shockwave Medical Inc; and is on the Advisory Board for Shockwave Medical Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Transradial secondary access (TR-SA) may serve as an alternative to the traditional femoral secondary access (TF-SA) for pigtail placement in transcatheter aortic valve replacement (TAVR)., Objectives: The aim of this study was to assess the incidence of secondary access-related vascular complications after TR-SA or TF-SA in TAVR., Methods: The PULSE (Plug or sUture based vascuLar cloSurE after TAVR) registry retrospectively evaluated data of 10,120 patients who underwent transfemoral TAVR at 10 heart centers from 2016 to 2021. We compared TR-SA and TF-SA groups of 8,851 patients with available data regarding the secondary access location and validated observed data in 1:1 propensity score matching. Outcomes were evaluated according to Valve Academic Research Consortium 3 definitions., Results: The median age was 82.0 ± 6.9 years, and 49.1% (4,346/8,851) of patients were female. TR-SA was selected in 1,686 patients (19.0%) and TF-SA in 7,165 (81.0%) overall. Vascular complications at the secondary access occurred in 0.3% (5/1,686 [TR-SA]) vs 3.2% (232/7,165 [TF-SA]; P < 0.001) and were considered major in 0.2% (3/1,686 [TR-SA]) vs 1.5% (109/7,165 [TF-SA]) and minor in 0.1% (2/1,686 [TR-SA]) vs 1.7% (123/7,165 [TF-SA]; P < 0.001 for both). Surgical repair was required in 0 TR-SA patients and in 0.9% (66/7,165) of TF-SA patients. Primary access vascular complications were similar (11.6% (196/1,686 [TR-SA]) vs 11.5% (825/7,165 [TF-SA]); P = 0.93); bleeding type III/IV occurred less with TR-SA (2.5% [42/1,686] vs 4.7% [334/7,165] with TF-SA; P < 0.001). After propensity score matching, secondary access-related vascular complication rates remained lower for TR-SA (0.2% [1/512] vs 2.9% [15/512] for TF-SA; P < 0.001)., Conclusions: During transfemoral TAVR, TR-SA was associated with lower rates of access site complications and severe bleeding compared to TF-SA. In fact, secondary access-related complications were 10× higher for TF-SA and frequently required invasive treatments. These findings challenge the fact that most TAVR procedures are still performed with TF-SA., Competing Interests: Funding Support and Author Disclosures Dr Kim has received personal fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Meril Life Sciences, and Shockwave Med. Dr Adam has received consultancy or speaker fees from Abbott, Boston Scientific, Edwards Lifesciences, JenaValve, and Medtronic; and is a proctor for Abbott, JenaValve, and Medtronic. Dr Braun has received speaker fees from Abbott Vascular and Edwards Lifesciences. Dr Tamm has received consultancy or speaker fees from Edwards Lifesciences, JenaValve, and Medtronic; and is a proctor for JenaValve. Dr Bleiziffer has received speaker fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Leistner has received speaker and advisory fees from Abbott. Dr Dreger has received proctoring, speaker, and advisory fees from Abbott and Edwards Lifesciences; and has received research support from Abbott. Dr Conradi has received advisory fees from Abbott, Medtronic, and JenaValve; and has received consulting fees from Edwards Lifesciences, Boston Scientific, MicroPort, PiCardia, MicroInterventions, VenusMedtech, and Smartcanula Sàrl. Dr Schäfer has received speaker fees and/or travel support from Edwards Lifesciences, Abbott, and Boston Scientific unrelated to the submitted work. Dr Geyer has received consultancy or speaker fees from Edwards Lifesciences; and is a proctor for JenaValve. Dr Rudolph has received speaker and advisory fees from Abbott, Edwards Lifesciences, JenaValve, Boston Scientific, Medtronic, and Amgen. Dr Seiffert has received speaker or advisory fees from Abbott Vascular, Abiomed, Amgen, AstraZeneca, Boston Scientific, Bristol Myers Squibb, Daichii-Sankyo, Edwards Lifesciences, Inari Medical, Medtronic, Pfizer, Shockwave Medical, and Siemens Healthineers; and has received a research grant from Boston Scientific all unrelated to the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Climatic oscillations are considered primary factors influencing the distribution of various life forms on Earth. Large species adapted to cold climates are particularly vulnerable to extinction due to climate changes. In our study, we investigated whether temperature increase since the Late Pleistocene and the contraction of environmental niche during the Holocene were the main factors contributing to the decreasing range of moose (Alces alces) in Europe. We also examined whether there were significant differences in environmental conditions between areas inhabited by moose in Europe and Asia, that could support the division of moose into western and eastern forms, as suggested by genetic and morphological data. We analysed environmental conditions in the locations of 655 subfossil and modern moose occurrences over the past 50,000 years in Eurasia. We found that the most limiting climatic factor for the moose distribution since the Late Pleistocene was July temperature. More than 90 % of moose records were found in areas where mean summer temperature was below 19 °C, with July temperatures showing over 3 times narrower interquartile range compared to January temperatures. We identified significant differences in environmental conditions between areas inhabited by the European and Asiatic moose. In Europe, the species occurred in regions with milder climates, higher primary productivity, and more frequently within forest biomes compared to Asiatic individuals. The moose range shifted more in the west-east than in the south-north direction during the Holocene climate warming in Europe. We conclude that although the area of suitable moose habitat has increased since 12-8 ka years BP, as demonstrated by environmental niche modeling, the retreat of A. alces in large areas of Europe was likely caused by anthropogenic landscape change (e.g., deforestation) and overhunting by humans during the late Holocene rather than by climate warming during the Pleistocene to Holocene transition., Competing Interests: Declaration of competing interest Due to the Ukrainian laws established since the Russian invasion in February 2022, Ukrainian scientists employed in the Ukrainian institutions are not allowed to be included as co-authors in the same papers with Russian researchers. That is why the name of professor Bogdan Ridush from the Yuriy Fedkovych Chernivtsi National University in Ukraine, who participated in this study, based on his request, has been excluded from the list of authors and moved to the Acknowledgements., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study investigated the concentration profiles and geographical variability of contaminants in house dust across Europe. A collaborative trial (CT) was organized by the NORMAN network using pooled dust and advanced chromatographic and mass spectrometric techniques combined with suspect screening and non-target screening (NTS). Over 1200 anthropogenic compounds were tentatively identified. Additionally, seventy-five individual samples were subjected to target analysis and NTS. The median concentrations of most contaminants varied <3-fold across Europe, and the contaminant profile of European dust was similar to that of North American dust, which was investigated in a previous CT. This similarity may be attributed to the use of similar consumer articles and building materials throughout the developed world. Multivariate data analysis revealed geographical trends in contaminant distribution, with north-south gradients across Europe. Geographical trends were more frequently found for compounds with rapid release (pharmaceuticals, personal care products, fragrances, pesticides, biocides) and smoke-related compounds. The concentrations of chlorinated paraffins, polycyclic aromatic hydrocarbons (PAHs), perfluorinated alkyl substances and stimulants generally increased from north to south, whereas the biocides levels decreased from north to south. Despite widespread presence of in-use contaminants in dusts, some of the highest risks come from compounds that have been restricted for decades or more. These include di(2-ethylhexyl) phthalate (DEHP), polychlorinated biphenyl (PCB) 118 and polybrominated diphenyl ethers 47, 99, and 153. DEHP remains the most abundant contaminant in European house dust, while the other compounds are classified as persistent organic pollutants (POPs). Moreover, there is a striking lack of reliable toxicity data, particularly for emerging compounds. For instance, although acceptable daily intakes (ADIs) were examined for 202 compounds, only 46 had consensus-based ADI values. The results highlight the need for proactive measures to prevent hazardous chemicals from entering the market and for careful selection of substitute chemicals, when such are needed, to avoid regrettable substitutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Pesticide applications in agriculture result in complex mixtures of Plant Protection Products (PPPs) in the environment. The ecotoxicological effects of these mixtures can occur at concentrations considered safe for individual chemicals, indicating potential risks underestimated by current regulatory assessments focused on individual active ingredients. To address this challenge, our study introduces a methodology for identifying priority PPPs for formulating mixtures, enabling further ecotoxicological testing in water and sediment compartments of edge-of-field surface water bodies, targeting pelagic and benthic organisms. This methodology was primarily based on the actual quantification of PPPs present in these compartments from selected case study sites (CSSs) in Europe and Argentina (11 and 4 for water and sediments, respectively). A conceptual framework was developed that discriminates and selects concerning PPPs based on their individual risk quotient and frequency of occurrence in each CSS, drawing upon two EU regulatory risk assessment approaches, i.e., the general approach under REACH for any environmental contaminant of concern - the European Chemicals Agency (ECHA) approach; and that specifically focusing on PPPs - the European Food Safety Authority (EFSA) approach. Irrespective of whether the focus is on water or sediments, the study revealed disparities in PPP rankings depending on the approach used to identify PPPs of concern, with the ECHA approach being more conservative than the EFSA approach. Despite this, the EFSA approach follows a more standardized assessment factor definition strategy, potentially allowing avoidance of risk overestimation, as well as resulting in a more balanced representation of different PPP classes for subsequent mixtures testing. Overall, the methodological development reported herein, along with the inconsistencies found when comparing different regulatory approaches to assess the risk of environmental contaminants, highlight the need for further discussion on the most appropriate directions towards the standardization of the regulatory risk assessment of PPP mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Evidence suggests that air pollution modifies the association between heat and mortality. However, most studies have been conducted in cities without rural data. This time-series study examined potential effect modification of particulate matter (PM) and ozone (O 3 ) on heat-related mortality using small-area data from five European countries, and explored the influence of area characteristics., Methods: We obtained daily non-accidental death counts from both urban and rural areas in Norway, England and Wales, Germany, Italy, and the Attica region of Greece during the warm season (2000-2018). Daily mean temperatures and air pollutant concentrations were estimated by spatial-temporal models. Heat effect modification by air pollution was assessed in each small area by over-dispersed Poisson regression models with a tensor smoother between temperature and air pollution. We extracted temperature-mortality relationships at the 5th (low), 50th (medium), and 95th (high) percentiles of pollutant distributions. At each air pollution level, we estimated heat-related mortality for a temperature increase from the 75th to the 99th percentile. We applied random-effects meta-analysis to derive the country-specific and overall associations, and mixed-effects meta-regression to examine the influence of urban-rural and coastal typologies and greenness on the heat effect modification by air pollution., Results: Heat-related mortality risks increased with higher PM levels, rising by 6.4% (95% CI: -2.0%-15.7%), 10.7% (2.6%-19.5%), and 14.1% (4.4%-24.6%) at low, medium, and high PM levels, respectively. This effect modification was consistent in urban and rural regions but more pronounced in non-coastal regions. In addition, heat-mortality associations were slightly stronger at high O 3 levels, particularly in regions with low greenness., Conclusion: Our analyses of both urban and rural data indicate that air pollution may intensify heat-related mortality, particularly in non-coastal and less green regions. The synergistic effect of heat and air pollution implies a potential pathway of reducing heat-related health impacts by improving air quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Substituting brown rice for white rice can increase the carcinogenic risk of inorganic arsenic (iAs) exposure, given that brown rice has a higher iAs content than white rice. This study estimated changes in the incremental lifetime cancer risk (ILCR) of iAs exposure from rice with increases in the proportion of brown to total rice consumption (PBT) in five regions around the world, including North America, Latin America, Europe, Asia, and Oceania. The results demonstrated that the magnitude of the increase in the ILCR of iAs exposure from rice expressed as an increase in PBT, ranged from 0.02 to 0.43 per 10,000 people for each 10 % increase in PBT. The highest increase was observed in Asia, followed by Latin America, North America, Oceania, and Europe. The daily rice consumption rate rather than the increase in iAs content is the critical factor responsible for regional differences in higher carcinogenic risk with increased PBT. This study also suggests that when considering the carcinogenic risks of iAs exposure from rice, substituting brown rice for white rice is feasible in North America and Europe but not in Asia and Latin America, while in Oceania, a partial substitution of brown rice for white rice (<55 %) is feasible., Competing Interests: Declaration of competing interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Widespread use of ciprofloxacin (CIP) in surface waters has raised ecological and human health concerns. However, the measured environmental concentration (MEC) of CIP may not directly indicate its ecological impact because CIP bioavailability and thus toxicity are influenced by environmental factors, such as pH and dissolved organic carbon (DOC). The present study integrates CIP toxicity as a function of pH and DOC into an environmental risk assessment (ERA) of CIP in European surface waters. A bioavailability model and water quality databases were used to estimate the predicted no-effect concentration (PNEC ECO ) of CIP to protect freshwater ecosystems under five ERA scenarios. PNEC ECO values were predicted following the European Medicines Agency guidelines using ecotoxicity data for the cyanobacterium Microcystis aeruginosa, identified as the freshwater species most sensitive to CIP. The PNEC ECO values predicted under Scenarios 1 (not considering bioavailability) and 2 (assuming the most bioavailable form of CIP, the zwitterion CIP +/- at maximum relative abundance) were 25 ng L -1 and 32 ng L -1 , respectively. Including the bioavailability effect of pH in Scenario 3 resulted in a range of PNEC ECO values from 25.0 to 62.4 ng L -1 (across Europe) whereas further including weak (Scenario 4) and strong (Scenario 5) CIP-DOC binding led to larger regional variations in PNEC ECO (25.8-1207 ng L -1 ). The PNEC ECO values were combined in Monte Carlo simulations with MEC data for the CIP to assess the probabilities of unacceptable risk (P UR ), uncertain risk (P UN ), and acceptable risk (P AR ) for Europe and for ten countries. The EU-wide P UR values (9.8 %-22.0 %) were unrepresentative of individual countries (0 %-99 %), while variations in P UR across scenarios (0 %-95 %) indicated different influences of pH and DOC by country. Overall, DOC has a stronger impact than pH on the predicted no-effect concentrations (PNECs) and on the ecological risk of CIP, and thus the consideration of bioavailability can greatly improve the environmental relevance of the ERA outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Climate change is exacerbating forest disturbances through more frequent and more intense droughts and fires, undermining their ability to recover from such disturbances. The response of fast-growing early-successional species to drought is poorly understood, despite their key role in ecological succession and their ability to enhance ecosystem resilience. Here, we compared the growth responses to drought events of three early-successional species (silver birch, black poplar, and Scots pine) with that of one late-successional species (European beech) across their natural distribution ranges in Europe. We used tree-ring widths of 6340 trees from 109 forest sites to establish species-specific tree-ring chronologies. We then used multiple linear regression to analyze which climatic or growth variables (pre-drought growth and growth during drought) best explained the tree responses to drought. Silver birch, Scots pine, and black poplar showed superior drought tolerance, with a slight, non-significant growth reduction under drought, whereas European beech showed a significant decrease in growth. The variables that influenced growth during and after the drought were species-specific. Annual precipitation and growth variables were key predictors of post-drought growth for Scots pine, black poplar, and European beech. Scots pine and silver birch grew better with increasing latitude, i.e., in Northern Europe than in Central Europe, while European beech and black poplar showed more growth at sites with high precipitation during the vegetation and dormant period, respectively. This study provides insights into the drought tolerance of early-successional species and highlights their ability to promote ecological succession and facilitate the transition to drought-resistant, late-successional forest ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The Arctic Oscillation (AO), North Atlantic Oscillation (NAO), and Pacific-North American Pattern (PNA) cause climate variability in the Northern Hemisphere (NH), which affects the carbon cycle of terrestrial ecosystems. Based on a dynamic global vegetation model, we analysed the impacts of the AO, NAO and PNA on changes in terrestrial climate and carbon cycle dynamics from 1980 to 2017. The positive AO (pAO), positive NAO (pNAO), and positive PNA (pPNA) mainly led to warmer and more humid conditions in the North Asia (NA) and Europe (EUR), whereas the negative AO (nAO), negative NAO (nNAO), and negative PNA (nPNA) resulted in colder and drier conditions. Furthermore, the nAO, nNAO, and nPNA increased the carbon sinks of terrestrial ecosystems, whereas the pAO, pNAO, and pPNA reduced the carbon sinks, especially in EUR. We also quantified the direct impacts of the oscillations in the concurrent season and their legacy impacts from the preceding season separately. Increased AO and NAO indices increased the carbon sinks in the East Asia (EA) and EUR, whereas an increased PNA index reduced the carbon sinks in most parts of the NH. With respect to legacy impacts, increased AO and PNA indices enhanced the carbon sinks in the Central-Western Asia and North Africa (CWN), Temperate North America (TNA) and Boreal North America (BNA), whereas an increased NAO index strengthened the carbon source capacity in the CWN, EUR, TNA, BNA. These results provide a framework for conducting further research on the mechanisms of interannual variability of the terrestrial carbon cycle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Atrial secondary tricuspid regurgitation (A-STR) has been proposed as an important etiologic subentity of secondary tricuspid regurgitation (STR). Patients with A-STR are frequently treated using transcatheter tricuspid valve edge-to-edge repair (T-TEER)., Objectives: The aims of this study were to evaluate prevalence and outcomes following T-TEER for severe A-STR and to compare the results to patients with nonatrial STR., Methods: The study included patients from the EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation) registry who underwent T-TEER for STR from 2016 until 2022. A-STR was defined as a ratio of end-systolic right atrial area to right ventricular area ≥1.5 in the presence of preserved right ventricular function (tricuspid annular plane systolic excursion >17 mm). The primary study endpoint was 2-year survival free from heart failure hospitalization. Secondary endpoints were 2-year survival, tricuspid regurgitation (TR) reduction at discharge and 1-year follow-up as well as changes in NYHA functional class., Results: This study included 641 patients (50% women) with a mean age of 79 ± 7 years. The overall prevalence of A-STR was 31% (n = 196). A-STR was associated with a higher prevalence of atrial fibrillation, less frequent comorbidities, better biventricular function, less leaflet tenting, and larger atria. Although TR severity was comparable at baseline, patients with A-STR had more effective procedural TR reduction (TR ≤2+ in 86.9% vs 80.4% of those with nonatrial STR; P = 0.005). Although NYHA functional class improved in both STR subetiologies, the symptomatic burden was lower in patients with A-STR at the latest available follow-up (NYHA functional class ≥III in 46% of patients with nonatrial STR vs 38% in those with A-STR; P = 0.033). Beyond that, A-STR was associated with higher 2-year survival rates free from heart failure hospitalization (66.3% [Q1-Q3: 58.2%-75.5%] vs 47.5% [Q1-Q3: 41.7%-54.7%] in patients with nonatrial STR; P < 0.001). Median survival follow-up was 379 days [Q1-Q3: 155-697 days]., Conclusions: A-STR is a common phenotype of STR and is associated with effective TR reduction and symptomatic reduction after T-TEER., Competing Interests: Funding Support and Author Disclosures Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Kresoja has received travel expenses from Edwards Lifesciences. Dr von Stein has received lecture honoraria from Edwards Lifesciences. Dr Rottbauer has received speaker honoraria Edwards Lifesciences and Abbott. Der Denti has served as a consultant for InnovHeart, Pi-Cardia, HVR, and Approxima; and has received speaker honoraria from Abbott and Edwards Lifesciences. Dr Rassaf has received speaker honoraria and consulting fees from AstraZeneca, Bayer, Pfizer, and Daiichi-Sankyo. Dr Barreiro-Perez has received speaker fees from Abbott Vascular, Edwards Lifesciences, and Venus Medtech. Dr Adamo has received consulting fees in the past 3 years from Abbott Structural Heart and Edwards Lifesciences. Dr von Bardeleben has received institutional grants from and served as a speaker for Abbott Vascular and Edwards Lifesciences. Dr Toggweiler has received personal honoraria from Medtronic, Boston Scientific, Biosensors, Abbott Vascular, Medira, Shockwave Medical, Teleflex, atHeart Medical, Cardiac Dimensions, Polares Medical, Amarin, Sanofi, AstraZeneca, ReCor Medical, and Daiichi-Sankyo; has received institutional research grants from Edwards Lifesciences, Boston Scientific, Fumedica, Novartis, and Boehringer Ingelheim; and holds equity in Hi-D Imaging. Dr Metra has received consulting fees in the past 3 years from Abbott Structural Heart, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics. Dr Geisler has received speaker honoraria and research grants from AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Ferrer/Chiesi, Medtronic, and Edwards Lifesciences (all unrelated to this study). Dr Estévez-Loureiro has received speaker fees from Abbott Vascular, Edwards Lifesciences, Boston Scientific, and Venus Medtech. Dr Lüdike has received speaker honoraria and consulting fees from AstraZeneca, Bayer, Pfizer, and Edwards Lifesciences; and has received research honoraria from Edwards Lifesciences. Dr Maisano received grant and/or research institutional support from Abbott, Medtronic, Edwards Lifesciences, Biotronik, Boston Scientific, NVT, Terumo, and Venus Medtech; has received consulting fees and personal and institutional honoraria from Abbott, Medtronic, Edwards Lifesciences, Xeltis, Cardiovalve, Occlufit, Simulands, Mtex, Venus, Squadra, and Valgen; has received royalty income from and holds intellectual property rights with Edwards Lifesciences; and is a shareholder (including share options) in Magenta, Transseptal Solutions, and 4Tech. Dr Praz has received travel expenses from Edwards Lifesciences, Abbott Vascular, Polares Medical, Medira, and Siemens Healthineers. Dr Kessler has received speaker honoraria from Edwards Lifesciences and Abbott. Dr Kalbacher has received personal fees from Abbott Medical, Edwards Lifesciences, Pi-Cardia, and Medtronic. Dr Rudolph has received research grants from Abbott Medical, Boston Scientific, and Edwards Lifesciences. Dr Iliadis has received consultant fees and travel expenses from Abbott Medical and Edwards Lifesciences. Dr Lurz has received institutional grants from Edwards Lifesciences; and has received honoraria from Innoventrics. Dr Hausleiter has received research grant support and speaker honoraria from Edwards Lifesciences. Dr Sticchi has served on an advisory board for Edwards Lifesciences. Dr Tarantini has received speaker fees from Abbott Vascular and Edwards Lifesciences. Dr Karam has received consultant fees from Edwards Lifesciences, Boston Scientific, and Medtronic; and has received proctor fees from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The extensive use of antibiotics in human and veterinary medicine has led to the emergence of antibiotic contaminants in the environment, posing significant risks to ecosystems and public health. This contamination arises from the persistence of antibiotics in aquatic environments, particularly in aquifer systems, where they contribute to the growing threat of antibiotic resistance. Despite increasing research, the understanding of the ecological and human health implications of these contaminants remains incomplete. Since these compounds are only partially removed by conventional wastewater treatment plants (WWTPs), they are continuously released into the environment. Antibiotics enter the environment mainly through human and animal excretions, improper drug disposal, wastewater treatment plants, and waste streams from antibiotic production. Recent research has focused on antibiotic metabolites and transformation products, which can affect aquatic ecosystems and the food chain, posing long-term risks to human health. This critical review provides a comprehensive analysis of the risk assessment of veterinary antibiotics (VAs) in European aquatic environments, where VAs concentrations ranging from micrograms to milligrams per liter. By examining toxicity data from freshwater and saltwater species, the study evaluates acute and chronic effects across different antibiotic classes. The review also assesses the sensitivity of various taxonomic groups and species to different antibiotics, providing insights into potential ecological risks. Species sensitivity distributions and hazard concentrations affecting a given percentage of species are calculated to assess the overall ecological risk. The findings reveal varying proportions of toxicity data across antibiotic classes, with Aminoglycosides, β-lactams, Fluoroquinolones, Macrolides, and Tetracyclines classes demonstrating higher toxicity levels than others towards certain cyanobacteria and chlorophyta species. Macrolides and Fluoroquinolones emerge as particularly concerning due to their high toxicological risks across various aquatic environments. The analysis underscores the urgent need for further research to fill knowledge gaps and develop effective strategies to mitigate the harmful effects of VAs on aquatic ecosystems and human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Iron (Fe) deficiency-related chlorosis (lime chlorosis) and the "paradox of iron chlorosis" in calcicole and calcifuge plants are unresolved problems. We performed a meta-analysis of our previous studies to determine whether calcicoles are more resistant to lime chlorosis than calcifuges are, whether lime chlorosis is Fe chlorosis per se and what is the source of the "paradox of iron chlorosis" in grassland plants. We found that both calcicoles and calcifuges are susceptible to chlorosis when grown on alkaline soil. In general, lime chlorosis does not result from Fe deficiency but is likely associated with manganese (Mn). Additionally, our analyses revealed that Ecological Indicator Values for Europe for soil reaction (R EIVEs) are not random to experimentally determined calcicole/calcifuge behavior but are not straightforward. Ultimately, neither the experimentally determined calcicole index nor the R EIVEs explained the microelemental nutrition of grassland plants in general (except for Zn acquisition), which highlights the need for species ecology-oriented studies to understand these phytocenoses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The effect of unprecedented climate change conditions on the environment has attracted the attention of experts from various disciplines who wish to predict its evolution. This is due to its interaction with population health and people's quality of life. The emergence of vector-borne diseases (VBD) in Europe, particularly caused by invasive mosquitoes, has resulted in autochthonous transmission of Dengue and Chikungunya virus cases. In this contribution, we delve into the significant decline in the population of tiger mosquitoes and the noticeable reduction in their size, related to the changes that occur often in years with low rainfall and high temperatures during the summer months. This change can be traced to the morphology of the species, which has been analysed in this work and related to the possible enhanced transmission efficiency and susceptibility of vectors to VBD dissemination. Due to the greater susceptibility to pathogen replication and subsequent transmission of the pathogens to a host during blood feeding, these morphologically distinct species relatively seem to be an efficient vector. The relationship between the sizes of studied mosquitoes and rainfall levels requires more research by mathematical epidemiologists., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The criteria for ASD closure in patients with PAH are different between the AHA/ACC and the ESC guidelines. We aimed to study the prevalence of patients with different guideline criteria for ASD closure and its impact on the clinical outcome after closure., Methods and Results: A retrospective cohort study recruiting patients who underwent ASD closure from 2011-2020 was conducted in a single university hospital. Patients were grouped into ASD closure recommended (class I, class IIa, and class IIb) and ASD closure not recommended groups (class III). The primary outcome was the prevalence of patients with discordant criteria and the clinical outcomes and echocardiographic parameters after ASD closure. A total of 17 of 66 ASD patients (25.8 %) were diagnosed with ASD with pulmonary hypertension. Two patients were excluded due to incomplete right heart catheterization data. 13 patients (86.7 %) were classified as ASD-closure recommended group by both guidelines. Two patients, classified as class IIb by ACC/AHA guidelines, were unsuitable for ASD closure by ESC guidelines. After ASD closure, all 15 patients reported functional class improvement and no significant difference in the echocardiography parameters. However, the number of patients with a low probability of PHT was higher in patients with ESC guideline-recommended closure., Conclusions: Most patients (86.7 %) are in concordant classification regarding ASD closure recommendations. The ESC guidelines are more restrictive than the AHA/ACC guidelines, allowing fewer patients for ASD closure. However, the clinical outcomes after ASD closure are not significantly different between these guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Psychedelic drug therapy has gained prominence for its potential in treating various mental health conditions, including depression, post-traumatic stress disorder (PTSD), and anxiety. Psychedelic treatment differs from conventional psychiatric approaches in mode of action, legal status, and treatment approach. This work delves into the therapeutic potential, mechanisms, and regulatory approvals of key psychedelic substances like psilocybin, 3,4-Methyl enedioxy methamphetamine (MDMA), mescaline, ketamine, and Lysergic acid diethylamide (LSD). It also provides an overview of legal aspects, and regulations surrounding psychedelics in the US & Europe, emphasizing their Schedule I classification due to potential misuse. The United States Food & Drug Administration (USFDA) closely monitors psychedelics, employing expedited pathways for evaluation. Further, recent guidance from the FDA on considerations for clinical Investigations supports the safe development of psychedelics for human welfare. European Medicines Agency (EMA) regulators focus on atypical psychedelics, addressing challenges in safety and efficacy. Marketed products, such as Spravato nasal spray, face limited distribution due to safety concerns. The call for careful regulation and legislation is essential for harnessing psychedelics' potential for therapeutic benefits and human welfare., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although our understanding of the dramatic worldwide loss of biodiversity in recent decades is far from adequate, one of the main factors in areas dominated by agriculture is undoubtedly the widespread use of synthetic pesticides. Unfortunately, the ecological risk assessment (EcoRA) for pesticides is based on a few single-species bioassays which do not allow for the evaluation of risks to whole communities. Here we present the results of an experimental assessment of the risk to the ecosystem service provider (ESP) communities - pest control agents - from exposure to the commonly used pyrethroid insecticide, λ-cyhalothrin. The study was performed in five European countries (Germany, Poland, Portugal, Spain, United Kingdom) representing different pedoclimatic zones. Representatives of the most common species of the ESP communities in each country were exposed in a standardized insecticide-coated glass vials bioassay to five doses of λ-cyhalothrin: 0.8 %, 4 %, 20 %, 100 %, and 200 % of the recommended field dose (RFD) plus an untreated control. Based on the calculated LD 50 s, species sensitivity distributions (SSDs) were estimated for each country and on combined data. In all five countries, the estimated hazardous concentration for 5 % of the species (HD5) was between 0.23 % and 1.67 % RFD, with HD5 = 0.44 % RFD based on combined data. At the RFD = 7.5 g a.i./ha (active ingredient per hectare), the predicted affected fraction of the ESP communities was between 96.4 % and 99.9 % of the species (98.5 % for combined data). The results indicate an extremely high risk to ESP communities across Europe associated with the use of λ-cyhalothrin at the recommended doses when these species are exposed to insecticide treatment. We recommend that EcoRA should include multi-species approaches, such as SSD, to better protect entire ESP communities from the negative impacts of pesticides., Competing Interests: Declaration of competing interest Ryszard Laskowski reports financial support was provided by European Union. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Humans have selectively bred domestic pigeons (Columba livia domestica) to create breeds with a diversity of shapes, colors and other attributes. Since Darwin, the domestic pigeon has always been a popular model species for scientific research because of its richness of form, colouration and behaviour. It is believed that the world's squab pigeon industry uses breeds and hybrids from the Mediterranean region. An exception is the indigenous giant pigeon breeds of the Carpathian Basin, whose origin is not known. Therefore, our aims were 1) to understand the phylogenetic relationships of giant pigeons, which sheds light on the origin of Hungarian breeds and their relationship to the Mediterranean giant pigeon breed group; 2) to contribute molecular genetic data to the genealogy of 2 Iraqi pigeon breeds close to the pigeon domestication center, including the culturally important Iraqi Red Pigeon, and 3) to compare the genetic diversity of European and Middle Eastern domestic pigeon populations and to draw conclusions on the phylogenetic relationships between pigeon breeds and molecular clues to their different breeding practices of both regions. A 655-bp-long sequence of the cytochrome oxidase 1 (COI) region of the mitochondrial DNA was studied in a total of 276 pigeons (19 breeds). A total of 27 haplotypes were found, of which 22 were unique. The highest genetic diversity was found in the Carpathian Basin, and the lowest in the Iraqi region. STRUCTURE analysis revealed low structurality, K=3 was the most likely. The majority of the samples belong to the most ancient haplotype H&#95;2=219, however the Jacobin pigeon is on a very separate evolutionary branch with a large number of mutations. None of the 19 breeds investigated in this study have been previously studied in phylogenetics, and most of these breeds have potential as squab pigeons, and have good meat forms for utilization, therefore the results of this study may also be of help to the squab pigeon industry., Competing Interests: DISCLOSURES The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katalin Balog reports financial support was provided by Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund (Hungary). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The perspective explores the emergence of autochthonous tropical diseases in Europe, driven by climate change and the associated increase in vector-borne diseases. Rising temperatures, along with changes in humidity and rainfall patterns, have altered the activity, distribution, and diversity of vectors such as mosquitoes and ticks. Species like Aedes albopictus and Aedes aegypti, which are primary vectors of dengue, have established self-sustaining populations across Europe. This spread has led to a surge in cases of dengue fever, West Nile virus, and tick-borne encephalitis in temperate regions. The complexity of predicting these outbreaks is compounded by factors like vector diapause, serological cross-reactivity, and land-use changes. The perspective calls for the implementation of enhanced surveillance, weather-linked predictive models, and robust vector control strategies to mitigate the public health risks posed by the spread of these diseases. As climate change accelerates, Europe faces increasing health threats previously confined to tropical regions, emphasizing the need for proactive public health measures to protect populations from this growing threat., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Climate change affects plant species, especially those with restricted ecology and distribution. Centaurium erythraea is a flowering plant species in the Gentianaceae family, native to Europe, with its centre of diversity in the Mediterranean and western Asia. Of the 11 infraspecific taxa distinct from C. erythraea, only two are common in Europe: C. erythraea subsp. erythraea (widespread nominal subspecies) and C. erythraea subsp. majus (mainly distributed in the western Mediterranean region). Freshly collected samples of 36 plants from 11 localities across Lower Silesia (Central Europe) were utilised for taxonomic and genetic analysis. The barcode sequences of chloroplast DNA region matK were used for molecular analysis. Data deposited in GenBank was also used. Five haplotypes were identified among the analysed specimens. Species Distribution Modelling (SDM) techniques were applied to predict the current and future (short- and long-term projections) potential distribution of C. erythraea subsp. majus and to identify the most influential climatic factors. Despite the typical Mediterranean distribution, the presence of C. erythraea subsp. majus outside its natural range in SW Poland has been confirmed by morphological and genetic studies. The mean monthly precipitation of the wettest quarter and the mean daily temperatures of the warmest quarter were identified as the key climatic factors. Short-term scenarios suggest that C. erythraea subsp. majus will maintain most of its current suitable habitats and potentially expand into the lowlands of Central Europe. However, long-term projections indicate a potential reduction in its currently suitable areas, especially in the southern parts of its range, with a possible expansion into north-western Europe. The results of these studies provide clear evidence of the impact of ongoing climate change on species range changes. These findings suggest that climate change may create new opportunities for Mediterranean species to spread to new regions, using C. erythraea subsp. majus as an example., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Limited data are available to guide the management of coronary artery aneurysms (CAAs)., Objectives: The authors sought to define the clinical characteristics, identify variables that predict outcomes, and provide long-term data on CAAs., Methods: We describe outcomes from 1,729 consecutive patients with CAAs included in an ambispective international registry (CAAR [Coronary Artery Aneurysm Registry]; NCT02563626) involving 33 hospitals across 9 countries in America and Europe., Results: Patients were predominantly male (78.6%; 1,359/1,729) with a mean age of 66 years. Classic cardiovascular risk factors were common, as well as coronary artery disease (85.8%; 1,484/1,729), peripheral vascular disease (10.9%; 188/1,729), and chronic kidney disease (8.0%; 138/1,729). The median number of aneurysms per patient was 1.0 (Q1-Q3: 1.0-1.0), with the most affected territory being the left anterior descending artery (49.6%; 857/1,729). The majority underwent any revascularization procedure (68.5%; 1,184/1,729), mainly percutaneous coronary intervention (50.7%; 877/1,729), and were discharged on dual antiplatelet therapy (65.6%; 1,134/1,729). After a median follow-up of 44.8 months (Q1-Q3: 14.9-88.1), 379 died (21.9%), and 641 (37.1%) developed a major adverse cardiovascular event (MACE) (all-cause death, heart failure, unstable angina, and reinfarction). In a multivariable analysis, age (HR: 1.03; 95% CI: 1.02-1.04; P < 0.001), diabetes mellitus (HR: 1.47; 95% CI: 1.23-1.75; P < 0.001), renal insufficiency (HR: 1.53; 95% CI: 1.19-1.96; P = 0.010), peripheral vessel disease (HR: 1.43; 95% CI: 1.13-1.82; P = 0.003), reduced left ventricular ejection fraction (HR: 0.98; 95% CI: 0.98-0.99; P < 0.001), acute indication for the index coronary angiography (HR: 1.30; 95% CI: 1.08-1.55; P = 0.005), and the number of coronary vessels presenting severe stenosis (HR: 1.11; 95% CI: 1.02-1.20; P = 0.015) were independent predictors of MACEs. Remarkably, only 37 patients presented with local aneurysm complications during follow-up., Conclusions: The long-term prognosis of CAAs is not favorable, with MACEs associated with the underlying risk factor profile for atherosclerotic heart disease., Competing Interests: Funding Support and Author Disclosures This study was supported by an unconditioned grant from Fundación “Interhospitalaria para la” Investigación Cardiovascular (FIC). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The success of non-native species (NNS) invasions depends on patterns of dispersal and connectivity, which underpin genetic diversity, population establishment and growth. In the marine environment, both global environmental change and increasing anthropogenic activity can alter hydrodynamic patterns, leading to significant inter-annual variability in dispersal pathways. Despite this, multi-generational dispersal is rarely explicitly considered in attempts to understand NNS spread or in the design of management interventions. Here, we present a novel approach to quantifying species spread that considers range expansion and network formation across time using the non-native Pacific oyster, Magallana gigas (Thunberg 1793), as a model. We combined biophysical modelling, dynamic patch occupancy models, consideration of environmental factors, and graph network theory to model multi-generational dispersal in northwest Europe over 13 generations. Results revealed that M. gigas has a capacity for rapid range expansion through the creation of an ecological network of dispersal pathways that remains stable through time. Maximum network size was achieved in four generations, after which connectivity patterns remained temporally stable. Multi-generational connectivity could therefore be divided into two periods: network growth (2000-2003) and network stability (2004-2012). Our study is the first to examine how dispersal trajectories affect the temporal stability of ecological networks across biogeographic scales, and provides an approach for the assignment of site-based prioritisation of non-native species management at different stages of the invasion timeline. More broadly, the framework we present can be applied to other fields (e.g. Marine Protected Area design, management of threatened species and species range expansion due to climate change) as a means of characterising and defining ecological network structure, functioning and stability., Competing Interests: Declaration of competing interest Authors declare no known competing interests. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

The presence of pesticide residues in waterbed sediments poses a significant concern for aquatic ecosystems' health. This study examined pesticide contamination in sediments of 38 water bodies, embedded in agricultural-dominated regions, across eight European countries. Three indicators were targeted: occurrence, type, and concentrations of multiple pesticide residues in sediments. 196 pesticide residues (including degradation products) were tested in the sediment samples. The analytical results showed that only one sample was 'pesticide-free', three samples contained a single pesticide residue, and the remaining 34 samples contained mixtures of residues. Overall, 99 different residues were found in the sediments, with a maximum of 48 in a single sample. Twenty-seven out of the 99 detected residues were not approved for agricultural use at the time of sampling. The numbers of detected residues and pesticide levels varied among countries. AMPA, glyphosate and DDTs were the most common residues in sediment samples with frequencies of 76, 61, and 52%, respectively. The sediments from the Czech Republic had the highest pesticide concentrations, with total pesticide concentrations ranging between 600 and 1200 μg kg -1 . The lowest total pesticide concentrations were found in Slovenia, Switzerland, Croatia, and Denmark, ranging between 80 and 120 μg kg -1 . Sediments presented a mix of non-persistent and persistent compounds. Twelve of the detected pesticides are very persistent/stable in sediments, raising concerns about the long-term impacts of pesticides. Our study on the distribution of pesticide residues in European sediments provides valuable insights into the extent of pesticide contamination and possible risks of pesticides to water bodies' health. It also underlines the need for monitoring, research, and policy efforts to mitigate the impacts of pesticides, and to evaluate potential risks of re-use of dredged sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mitral valve transcatheter edge-to-edge repair (M-TEER) reduces secondary mitral regurgitation (MR) in heart failure and impacts survival in selected patients as demonstrated in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial. However, long-term outcome data after M-TEER under real-world conditions are lacking., Objectives: This study sought to assess long-term efficacy and survival after M-TEER in a large real-world registry., Methods: We analyzed patients with significant secondary MR undergoing M-TEER from the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) registry. Long-term MR reduction, functional outcomes, survival rate, and predictors for all-cause mortality were assessed., Results: In this study, 1,628 patients undergoing M-TEER (mean age 73.8 years, mean EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 6.9%, 86.6% NYHA functional class ≥III) with available long-term data were included. Five-year survival was 35.0%. Long-term MR reduction (MR grade ≤2+: baseline 4.1%, discharge 92.2%, 5-year follow-up 85.5%; P < 0.001) and functional improvement (NYHA ≤II: baseline 13.4%, 5-year follow-up 60.1%; P < 0.001) was observed. The degree of residual MR was associated with 5-year survival (residual MR grade ≤1+: 38.6%; 2+: 30.5%; ≥3+: 22.6%; P < 0.001). Independent predictors for 5-year all-cause mortality post-M-TEER included age, renal function, residual MR, NYHA functional class, left ventricular ejection-fraction, and COAPT trial eligibility (P < 0.01 for all)., Conclusions: This extensive multicenter registry underscores the long-term efficacy of M-TEER in real-world clinical practice and identifies predictors for long-term survival. These findings contribute valuable insights for optimizing patient selection in routine clinical interventions., Competing Interests: Funding Support and Author Disclosures Dr Stocker has served as consultant for Occlutech International and received speaker honoraria from Edwards Lifesciences. Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Weckbach has received speaker honoraria from AstraZeneca and Bayer. Dr Koell has received personal fees from Edwards Lifesciences. Dr Kalbacher has received personal fees from Abbott Medical, Edwards Lifesciences, Medtronic, and Pi-Cardia Ltd. Dr Hausleiter has received speaker honoraria from and served as a consultant for Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ambient air pollution has become a challenging global health issue since industrialization, especially affecting respiratory diseases. However, the causal link between air pollution and allergic respiratory diseases (ARDs) remains unclear due to confounding factors in conventional epidemiological studies across different populations. Thus, we aimed to clarify the causal associations between air pollution and ARDs in European and East Asian populations using Mendelian randomization (MR)., Methods: MR utilizes genetic variants and provides a satisfactory level of causal evidence. Genetic data for exposures (PM 2.5 , PM 2.5 absorbance, PM 10 , PM coarse , NO 2 and NO x ) and outcomes (allergic rhinitis, chronic rhinosinusitis, asthma, and obesity related asthma) were obtained from genome-wide association studies. Instrumental variables were strictly filtered based on core assumptions. Two-sample MR and sensitivity analyses were conducted separately for European and East Asian populations., Results: PM coarse was causally associated with an increased risk of chronic rhinosinusitis (OR = 1.588 [1.002-2.518]; p = 0.049) and obesity related asthma (OR = 1.956 [1.012-3.780]; p = 0.046) in European population, and PM 10 was associated with a decreased risk of allergic rhinitis in East Asian population (OR = 0.882 [0.798-0.974]; p = 0.013). No heterogeneity or pleiotropy was detected in any significant causal association., Conclusion: Our findings indicate that ambient air pollution has opposite impacts on the etiology of ARDs in European and East Asian populations, which provides evidence for decisions on public policies and suggests that different responses to environmental factors such as air pollution may contribute to racial heterogeneity of ARDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Plastic pollution has become a global concern, affecting many species around the world. While well-documented for marine ecosystems, the impact of plastic pollution on terrestrial ecosystems is comparatively limited. In fact, only recently have some studies begun to explore the occurrence, pathways, and impacts of plastic in the atmosphere and on terrestrial species. Here, we assess the presence of synthetic material in nests of three swift species breeding in the Western Palearctic: the common swift (Apus apus), the pallid swift (Apus pallidus), and the alpine swift (Tachymarptis melba). Using data from 487 nests spanning 25 colonies and seven European countries, we show that 36.5 % of the examined nests contained anthropogenic materials, mainly plastic debris. Notably, Pallid swifts' nests, with 85 % of the total nests examined with plastic, rank among birds with the highest plastic content in nests. We also demonstrate that the probability of finding plastic in the nest increased substantially with the human footprint of the landscape. Last, we recorded four cases of swifts entangled in their own nest, a low proportion compared to other species studied previously. Our study provides compelling evidence that plastic pollution may also be considered a concern for other terrestrial species, particularly for birds with highly aerial lifestyles, such as other swifts. The correlation with the human footprint suggests that areas with higher human activity contribute more significantly. Moreover, the entanglement cases, although low, indicate a threat to bird health and welfare. To our knowledge, our study is the first to report a direct interaction between floating plastic debris in the atmosphere and any species. Understanding this interaction is key, not only due to the lack of research on the topic, but also because it highlights that plastic pollution is a multifaceted environmental issue affecting various ecosystem categories, and the broader implications of atmospheric plastic circulation on wildlife and ecosystems health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

From the beginning of May 2023 to the end of August 2023, the Northern Hemisphere experienced significant wildfire activity with the most widespread fires occurring in Canada. Forest fires in Canada destroyed more than 15.6 million hectares of forests. These wildfires worsened air quality across the region and other parts of the world. The smoke reached southern Europe by the end of June 2023. To better understand the consequences of such forest fires far from the site of origin, aerosol optical, microphysical and radiative properties were analyzed during this event for southern Europe using data from the Visible Infrared Imaging Radiometer Suite (VIIRS), TROPOspheric Monitoring Instrument (TROPOMI), and Aerosol Robotic Network (AERONET). TROPOMI aerosol index (AI) and the carbon monoxide (CO) product confirm that the smoke originated directly from these forest fires. AERONET data from the El Arenosillo site in southern Spain showed maximum aerosol optical depth (AOD) values on June 27 reached 2.36. Data on Angstrom Exponent (AE), aerosol volume size distribution (VSD), single scattering albedo (SSA), fine mode fraction (FMF), volume particle concentration, effective radius (R Eff ), absorption AOD (AAOD), extinction AE (EAE) and absorption AE (AAE) showed that fine-mode particles with carbonaceous aerosols contribution predominated in the atmosphere above the El Arenosillo site. Direct aerosol radiative forcing (DARF) at the top (DARF TOA ) and bottom of atmosphere (DARF BOA ) were -103.1 and -198.93 Wm -2 , respectively. The atmospheric aerosol radiative forcing (DARF ATM ) was found to be 95.83 Wm -2 and with a heating rate 2.69 K day -1 , which indicates the resulting warming of the atmosphere., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In recent years, the oak lace bug, Corythucha arcuata, has emerged as a significant threat to European oak forests. This species, native to North America, has in the last two decades rapidly extended its range in Europe, raising concerns about its potential impact on the continent's invaluable oak populations. To address this growing concern, we conducted an extensive study to assess the distribution, colonization patterns, and potential ecological niche of the oak lace bug in Europe. We gathered 1792 unique presence coordinates from 21 Eurasian countries, utilizing diverse sources such as research observations, citizen science initiatives, GBIF database, and social media reports. To delineate the realized niche and future distribution, we employed an ensemble species distribution modelling (SDM) framework. Two future greenhouse gas scenarios (RCP 4.5 and RCP 8.5) were considered across three-time intervals (2021-2040, 2061-2080, and 2081-2100) to project and evaluate the species' potential distribution in the future. Our analysis revealed that significant hotspots rich in host species occurrence for this invasive insect remain uninvaded so far, even within its suitable habitat. Furthermore, the native ranges of Turkey oak (Quercus cerris L.) and Hungarian oak (Quercus frainetto L.) species offer entirely suitable environments for the oak lace bug. In contrast, the pedunculate oak and sessile oak distribution ranges currently show only 40 % and 50 % suitability for colonization, respectively. However, our predictive models indicate a significant transformation in the habitat suitability of the oak lace bug, with suitability for these two oak species increasing by up to 90 %. This shift underlines an evolving landscape where the oak lace bug may exploit more of its available habitats than initially expected. It emphasises the pressing need for proactive measures to manage and stop its expanding presence, which may lead to a harmful impact on the oak population across the European landscape., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Although many studies have discussed the impact of Europe's air quality, very limited research focused on the detailed phenomenology of ambient trace elements (TEs) in PM 10 in urban atmosphere. This study compiled long-term (2013-2022) measurements of speciation of ambient urban PM 10 from 55 sites of 7 countries (Switzerland, Spain, France, Greece, Italy, Portugal, UK), aiming to elucidate the phenomenology of 20 TEs in PM 10 in urban Europe. The monitoring sites comprised urban background (UB, n = 26), traffic (TR, n = 10), industrial (IN, n = 5), suburban background (SUB, n = 7), and rural background (RB, n = 7) types. The sampling campaigns were conducted using standardized protocols to ensure data comparability. In each country, PM 10 samples were collected over a fixed period using high-volume air samplers. The analysis encompassed the spatio-temporal distribution of TEs, and relationships between TEs at each site. Results indicated an annual average for the sum of 20 TEs of 90 ± 65 ng/m 3 , with TR and IN sites exhibiting the highest concentrations (130 ± 66 and 131 ± 80 ng/m 3 , respectively). Seasonal variability in TEs concentrations, influenced by emission sources and meteorology, revealed significant differences (p < 0.05) across all monitoring sites. Estimation of TE concentrations highlighted distinct ratios between non-carcinogenic and carcinogenic metals, with Zn (40 ± 49 ng/m 3 ), Ti (21 ± 29 ng/m 3 ), and Cu (23 ± 35 ng/m 3 ) dominating non-carcinogenic TEs, while Cr (5 ± 7 ng/m 3 ), and Ni (2 ± 6 ng/m 3 ) were prominent among carcinogenic ones. Correlations between TEs across diverse locations and seasons varied, in agreement with differences in emission sources and meteorological conditions. This study provides valuable insights into TEs in pan-European urban atmosphere, contributing to a comprehensive dataset for future environmental protection policies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The European Commission (EC) has tasked the European Medicines Agency (EMA) to provide a recommendation towards the acceptability of titanium dioxide (TiO 2 ) in pharmaceutical products by early 2024 to inform on final decision in early 2025[1]. Unlike the already implemented ban of TiO 2 in foods, removing this excipient from pharmaceutical products will likely have significant impact on the pharmaceutical industry, regulatory agencies, and patients. This commentary explores the challenges facing the pharmaceutical industry tasked with supporting the development and registration of TiO 2 free (TF) drug products. Specifically, justification of formulation changes and potential impact to in vitro and in vivo performance, as well as differences in global regulatory comparative dissolution requirements to justify changing to TF drug product are discussed. Particularly, the uncertainties around how a formulation change such as removal of TiO 2 from immediate release solid oral dosage forms will be viewed in Europe compared to other regions is discussed. To respond to these challenges and avoid disruption to the medicines supply chain in case in vitro data such as dissolution is either too challenging or insufficient to justify changing to TF product, pharmaceutical companies may have to decide if the level of risk is worth the effort needed to reformulate, develop, and register a new TF product., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the prevalence and associated risk indicators for dentine hypersensitivity (DH), erosive tooth wear (ETW), gingival recession (GR), and gingival inflammation (bleeding on probing, BOP), with clinical and questionnaire data from seven European countries., Methods: A cross-sectional, observational, seven-European country, epidemiological study in systemically healthy adults. Participants completed a questionnaire regarding oral hygiene, diet and lifestyle factors. A clinical examination, by calibrated examiners, measured DH (Schiff; participant yes/no), ETW (basic erosive tooth wear examination, BEWE), GR (mm), and BOP (yes/no)., Results: 3551 participants completed the study, mean age 44 ± 17.4, 43.6 % male, 26.1 % rural dwellers. DH (Schiff ≥ 1) was seen in 75.9 % of participants, ETW (BEWE ≥ 1) in 97.6 %, GR (≥1 mm) in 87.9 %. 65.7 % participants had BOP ≥ 10 % sites, 34.3 % BOP<10 % with probing depths ≤3 mm. DH, ETW, GR and BOP increased markedly during young adult life. Thereafter, GR and ETW continued to increase, DH declined after around age 38-47, and BOP plateaued after age 48. DH was significantly associated with ETW (p < 0.001) and GR (p < 0.01); GR was significantly associated with BOP on lingual surfaces (p = 0.017). There were significant associations between increased full mouth BOP ≥ 10 % and reduced brushing duration and exercise frequency (p < 0.001); increased DH and heartburn (p < 0.001); decreased DH (p < 0.001), ETW (p < 0.001) and BOP ≥ 10 % (p = 0.002) with powered toothbrush use., Conclusions: Prevalence of oral conditions assessed was high, greater than in the majority of the GR, DH and ETW literature. Periodontal health was seen in a third of sampled individuals. All these conditions varied markedly by country and age., Clinical Significance: Oral diseases and conditions were highly prevalent throughout the seven European countries investigated. For the majority, these conditions are eminently preventable and treatable by changing behaviours. Upstream policy changes are needed to address these health challenges, to raise awareness and to empower individuals with oral health education and support., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicola West reports financial support was provided by Haleon plc. Jonathan Creeth reports a relationship with Haleon plc that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The CTO-ARC (Chronic Total Occlusion Academic Research Consortium) recognized that a nonstandardized definition of chronic total occlusion (CTO) percutaneous coronary intervention approaches can bias the complications' attribution to each crossing strategy., Objectives: The study sought to describe the numbers, efficacy, and safety of each final CTO crossing strategy according to CTO-ARC recommendations., Methods: In this cross-sectional study, data were retrieved from the European Registry of Chronic Total Occlusions between 2021 and 2022., Results: Out of 8,673 patients, antegrade and retrograde approach were performed in 79.2% and 20.8% of cases, respectively. The antegrade approach included antegrade wiring and antegrade dissection and re-entry, both performed with or without retrograde contribution (antegrade wiring without retrograde contribution: n = 5,929 [68.4%]; antegrade wiring with retrograde contribution: n = 446 [5.1%]; antegrade dissection and re-entry without retrograde contribution: n = 353 [4.1%]; antegrade dissection and re-entry with retrograde contribution: n = 137 [1.6%]). The retrograde approach included retrograde wiring (n = 735 [8.4%]) and retrograde dissection and re-entry (n = 1,073 [12.4%]). Alternative antegrade crossing was associated with lower technical success (70% vs 86% vs 93.1%, respectively; P < 0.001) and higher complication rates (4.6% vs 2.9% vs 1%, respectively; P < 0.001) as compared with retrograde and true antegrade crossing. However, alternative antegrade crossing was applied mostly as a rescue strategy (96.1%)., Conclusions: The application of CTO-ARC definitions allowed the reclassification of 6.7% of procedures as alternative antegrade crossing with retrograde or antegrade contribution which showed higher MACCE and lower technical success rates, as compared with true antegrade and retrograde crossing., Competing Interests: Funding Support and Author Disclosures Dr Bufe has received speaker honoraria from Biotronik and Shockwave Medical. Dr Pyxaras has received consulting/speaker/proctorship honoraria from Abiomed, AstraZeneca, Asahi Intecc, Biotronik, Boston Scientific, and Terumo. Dr Ladwiniec has received consulting/speaker/proctoring honoraria from Abbott, Biotronik, Boston Scientific, Cordis, Shockwave Medical, and SMT. Dr Werner has received speaker honoraria from Abbott, Asahi Intecc, OrbusNeich, Philips, Siemens, and Terumo. Dr Mashayekhi has received consulting/speaker/proctoring honoraria from Abbott, Abiomed, Asahi Intecc, AstraZeneca, Biotronik, Boston Scientific, Cardinal Health, Daiichi-Sankyo, Medtronic, OrbusNeich, Shockwave Medical, Teleflex, and Terumo. Dr Ayoub has received consultant/proctor honoraria from Boston Scientific, Teleflex, Asahi Intecc, Cordis, Terumo, and SIS Medical. Dr Goktekin has received consulting/speaker/proctoring honoraria from Boston Scientific, Medtronik, MicroPort, and Asahi Inc. Dr Agostoni has received consulting honoraria from Abbott, Boston Scientific, Cordis, iVascular, Medtronic, Neovasc, Seven Sons, Teleflex, and Terumo. Dr Diletti has received consultant/proctoring honoraria from Asahi Intecc, Terumo, IMDS, Boston Scientific, Teleflex, and Philips. Dr Rathore has received honoraria for speaker and proctoring from Abbott Vascular and Translumina Therapeutics. Dr Bozinovic has served as a speaker or proctor and/or received honoraria from Orbus Neich and Medtronic. Dr Galassi has received consulting/speaker honoraria from Asahi Intecc and Ivascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A growing body of scientific literature stresses the need to advance current environmental risk assessment (ERA) methodologies and associated regulatory frameworks to better address the landscape-scale and long-term impact of pesticide use on biodiversity and the ecosystem. Moreover, more collaborative and integrative approaches are needed to meet sustainability goals. The One Health approach is increasingly applied by the European Food Safety Authority (EFSA) to support the transition towards safer, healthier and more sustainable food. To this end, EFSA commissioned the development of a roadmap for action to establish a European Partnership for next-generation, systems-based Environmental Risk Assessment (PERA). Here, we summarise the main conclusions and recommendations reported in the 2022 PERA Roadmap. This roadmap highlights that fragmentation of data, knowledge and expertise across regulatory sectors results in suboptimal processes and hinders the implementation of integrative ERA approaches needed to better protect the environment. To advance ERA, we revisited the underlying assumptions of the current ERA paradigm; that chemical risks are generally assessed and managed in isolation with a substance-by-substance, realistic worst-case and tiered approach. We suggest optimising the use of the vast amount of information and expertise available with pesticides as a pilot area. It is recommended to as soon as possible adopt a systems-based approach, i.e. within the current regulatory framework, to spark a step-wise transition towards an ERA framed at a system level of ecological and societal relevance. Tangible systems-based and integrative steps are available. For instance, the rich sources of existing data for prospective and retrospective ERA of pesticides could be used to reality-benchmark existing and new ERA methods. To achieve these goals, collaboration among stakeholders across scientific disciplines and regulatory sectors must be strengthened., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

End-stage kidney disease (ESKD) poses a high burden on patients and health systems. While numerous studies indicate an association between air pollution and chronic kidney disease, studies on ESKD are rare. We investigated the association of long-term exposure to nitrogen dioxide (NO₂), fine particulate matter (PM 2.5 ), black carbon (BC) and ozone (O 3 ) with ESKD incidence in two large population-based European cohorts. We followed individuals in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP) and the Italian Rome Longitudinal Study (RoLS) using dialysis and kidney transplant registries. Long-term exposure to pollutants was estimated at the home address using Europe-wide land use regression models at 100x100m scale. Hazard ratios (HR) were determined from Cox-proportional hazard models adjusted for individual and neighbourhood level confounders. We observed 501 events among 136,823 individuals in VHM&PP (mean age 42.1 years; crude incidence rate (IR) 0.14 per 1000 person-years) and 3231 events among 1,939,461 individuals in RoLS (mean age 52.4 years; IR 0.22 per 1000 person-years). In VHM&PP, there was no evidence of an association between PM 2.5 or O 3 and ESKD. There were elevated HRs but with large confidence intervals for BC (HR 1.17 [95 % confidence interval (CI): 0.98, 1.39] for 0.5*10 -5 /m), and for NO₂ (HR 1.14 [95%CI: 0.96, 1.35] for 10 μg/m 3 ). In RoLS, ESKD was associated with PM 2.5 (HR 1.37 [95 % CI: 1.06, 1.76] for an increase of 5 μg/m 3 ), while there was no evidence of association with BC, NO 2 , or O 3 exposure. Our study suggests an association of air pollution with ESKD incidence, which differed between the two cohorts and may possibly be influenced by respective air pollution mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)