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The environmental management cycles for chemicals and climate change (EMC 4 ) is a suggested conceptual framework for integrating climate change aspects into chemical risk management. The interaction of climate change and chemical risk brings together complex systems that are imperfectly understood by science. Making management decisions in this context is therefore difficult and often exacerbated by a lack of data. The consequences of poor decision-making can be significant for both environmental and human health. This article reflects on the ways in which existing chemicals management systems consider climate change and proposes the EMC 4 conceptual framework, which is a tool for decision-makers operating at different spatial scales. Also presented are key questions raised by the tool to help the decision-maker identify chemical risks from climate change, management options, and, importantly, the different types of actors that are instrumental in managing that risk. Case studies showing decision-making at different spatial scales are also presented highlighting the conceptual framework's applicability to multiple scales. The United Nations Environment Programme's development of an intergovernmental Science Policy Panel on Chemicals and Waste has presented an opportunity to promote and generate research highlighting the impacts of chemicals and climate change interlinkages. Integr Environ Assess Manag 2024;20:433-453. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

The Nordic Bioeconomy Pathways (NBPs), conceptualized subsets of Shared Socioeconomic Pathways varying from environmentally friendly to open-market competition scenarios, can lead to plausible stressors in future for using bioresources. This study analysed the impacts of NBPs on hydrology and water quality based on two different land system management attributes: management strategy and a combination of reduced stand management and biomass removal at a catchment-scale projection. To understand the potential impacts of NBPs, the Simojoki catchment in northern Finland was chosen, as the catchment mainly covered peatland forestry. The analysis integrated a stakeholder-driven questionnaire, the Finnish Forest dynamics model, and Soil and Water Assessment Tool to build NBP scenarios, including Greenhouse gas emission pathways, for multiple management attributes to simulate flows, nutrients, and suspended solids (SS). For the catchment management strategy, an annual decrease in nutrients was observed for sustainability and business-as-usual scenarios. Reduced stand management and biomass removal also led to decreased export of nutrients and SS for the same scenarios, whereas, in other NBPs, the export of nutrients and SS increased with decreased evapotranspiration. Although the study was investigated at a local scale, based on the current political and socioeconomic situation, the approach used in this study can be outscaled to assess the use of forest and other bioresources in similar catchments., (© 2023. The Author(s).)

Background: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS., Methods: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization., Results: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was ≥6 mm 2 in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P =0.45)., Conclusions: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03767621.

Development of cataracts is a well-known adverse effect of ionizing radiation, but little information is available on their incidence in patients after other medical procedures, such as cardiac catheterizations. The study objective was to determine the incidence of cataracts in a cohort of patients undergoing percutaneous coronary intervention (PCI) for chronic coronary total occlusion (CTO) and its association with radiation dose. The study analyzed the incidence of cataracts during the follow-up of 126 patients who underwent chronic total coronary PCI, using Cox regression to identify predictive factors of cataract development. The study included 126 patients, 86.9% male, with a mean age of 60.5 years (range, 55.0-68.0 years). Twenty-three (18.2% n = 23) developed cataracts during a mean follow-up of 49.5 months (range 37.3-64.5 months). A higher incidence was observed in patients who received more than 5 Gy (29.0% vs. 14.7%, Hazard ratio (HR = 2.84 [1.19-6.77]). Multivariate analysis revealed a relationship between cataract development during the follow-up and a receipt of radiation dose >5 Gy (HR = 2.60, 95% confidence interval [CI 1.03-6.61]; p = 0.03), presence or history of predisposing eye disease (HR = 4.42, CI:1.57-12.40), diabetes (HR = 3.33 [1.22-9.24]), and older age, as in >57 (HR, 6.40 [1.81-22.61]). An elevated incidence of cataracts was observed in patients after PCI for CTO. The onset of cataracts is related to the radiation dose during catheterization, which is a potentially avoidable effect of which operators should be aware.

Abstract: The aim of our study is to assess the impact of anemia, chronic kidney disease, and diabetes mellitus on platelet reactivity (PR) in patients with severe aortic stenosis, both at baseline and after transcatheter aortic valve implantation (TAVI). This study is a prespecified subanalysis of the REAC-TAVI prospective, multicenter trial that included patients pretreated with aspirin + clopidogrel before TAVI. PR was measured at baseline and at 5 different time points after TAVI with the VerifyNow assay (Accriva Diagnostics, San Diego, CA), over a 3-month follow-up period. Patients with high PR (HPR) at baseline, before TAVI (n = 48) were randomized to aspirin + clopidogrel or aspirin + ticagrelor for 3 months, whereas those with normal PR (NPR) (n = 20) were continued on aspirin + clopidogrel. A "raiser response" in PR was defined as an increase in PR units >20% of baseline after TAVI. Patients with HPR before TAVI presented concomitant anemia and chronic kidney disease more frequently than their counterparts with NPR. Anemia and higher body mass index were independently associated with HPR to clopidogrel at baseline. Moreover, anemic patients with baseline HPR who were continued on clopidogrel presented higher PR after TAVI than patients with HPR switched to ticagrelor. All patients with baseline NPR presented a "raiser response" after TAVI, which was nonexistent among patients with HPR managed with ticagrelor. In summary, anemia seems as a relevant factor associated with baseline HPR and higher PR after TAVI in patients with baseline HPR randomized to clopidogrel, whereas ticagrelor proved more effective than clopidogrel at attaining sustained reductions in PR during follow-up, regardless of baseline comorbidities., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Ticagrelor has proven more effective than clopidogrel at attaining a maintained suppression of high platelet reactivity (HPR) in aortic stenosis patients undergoing transcatheter aortic valve implantation (TAVI). This study aims to assess the influence of implanted valve type on the degree of platelet reactivity (PR) after TAVI., Methods: This study is a prespecified analysis of REAC-TAVI, a prospective, multicenter study that included patients on dual-antiplatelet therapy with aspirin and clopidogrel before TAVI. Patients with HPR (n = 48) were randomized to aspirin and clopidogrel or aspirin and ticagrelor for 3 months, while those without HPR (n = 20) were continued on aspirin and clopidogrel. PR was measured 6 hours, 24 hours, 5 days, 30 days, and 90 days after TAVI with VerifyNow assay. Bioprosthetic valves were classified as balloon-expandable valve (BEV), self-expandable valve (SEV), or other., Results: Sixty-eight patients comprising 32 BEVs, 28 SEVs, and 8 other valves were included. Devices were larger and postdilation was more frequent in the SEV group. Follow-up PR was lower in patients treated with ticagrelor vs those treated with clopidogrel at all time points after TAVI, including patients without baseline HPR (P<.001). PR after TAVI was similar in the three groups. Major cardiovascular adverse events, stroke, and hemorrhagic complications were comparable across the different bioprosthesis groups at 4-month follow-up., Conclusions: The effect of valve type on PR after TAVI is similar across the spectrum of most transcatheter valves. In our sample, ticagrelor achieved a faster and more effective reduction in PR than clopidogrel in patients with HPR undergoing TAVI, irrespective of valve type.

Climate change may affect stream ecosystems through flow regime alterations, which can be particularly complex in streams with a significant groundwater contribution. To quantify the impacts of climate change on hydrological regime and subsequently the stream biota, we linked SWAT-MODFLOW (A model coupling the Soil and Water Assessment Tool and the Modular Finite-difference Flow Model) with flow-biota empirical models that included indices for three key biological taxonomic identities (fish, macroinvertebrates and macrophytes) and applied the model-complex to a groundwater-dominated catchment in Denmark. Effects of predicted climate change towards the end of this century relative to the reference period (1996-2005) were tested with two contrasting climate change scenarios of different greenhouse gas emissions (Representative Concentration Pathway 2.6 (RCP 2.6) and RCP 8.5) and analysed for all subbasins grouped into streams of three size classes. The total water yield in the catchment did not change significantly (-1 ± 4 (SD) mm yr -1 ) from the baseline in the RCP2.6 scenario, while it increased by 9 ± 11 mm yr -1 in the RCP8.5 scenario. The three stream size classes underwent different alterations in flow regime and also demonstrated different biotic responses to climate change. All large and some small streams were impacted most heavily by the climate change, where fish and macrophyte indices decreased up to 14.4% and 11.2%, respectively, whereas these indices increased by up to 14.4% and 6.0%, respectively, in the medium and some small streams. The climate change effects were, as expected, larger in the RCP8.5 scenario than in the RCP2.6 scenario. Our study is the first to quantify the impacts of streamflow alterations induced by climate change on stream biota beyond specific 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 © 2020 Elsevier B.V. All rights reserved.)

Background: Transcatheter mitral valve repair (TMVR) could improve survival in functional mitral regurgitation (FMR), but it is necessary to consider the influence of left ventricular ejection fraction (LVEF). Therefore, we compare the outcomes after TMVR with Mitraclip ® between two groups according to LVEF., Methods: In an observational registry study, we compared the outcomes in patients with FMR who underwent TMVR with and without LVEF <30%. The primary endpoint was the combined one-year all-cause mortality and unplanned hospital readmissions due to HF. The secondary end-points were New York Heart Association (NYHA) functional class and mitral regurgitation (MR) severity. Propensity-score matching was used to create two groups with the same baseline characteristics, except for baseline LVEF., Results: Among 535 FMR eligible patients, 144 patients with LVEF <30% (group 1) and 144 with LVEF >30% (group 2) had similar propensity scores and were included in the analyses. The primary study endpoint was significantlly higher in group 1 (33.3% vs. 9.4%, p = 0.002). There was a maintained improvement in secondary endpoints without significant differences among groups., Conclusion: FMR patients with LVEF <30% treated with MitraClip ® had higher mortality and readmissions than patients with LVEF ≥30% treated with the same device. However, both groups improved the NYHA functional class and MR severity.

Assessing the impacts of groundwater abstractions on stream ecosystems is crucial for developing water planning and regulations in lowland areas that are highly dependent on groundwater, such as Denmark. To assess the effects of groundwater abstractions on flow regime and stream biota in a lowland groundwater-dominant catchment, we combined the SWAT-MODFLOW model with flow-biota empirical models including indices for three key biological taxonomic identities (fish, macroinvertebrates, and macrophytes). We assessed the effects of the current level of abstractions and also ran a scenario for assessing the effect of extreme groundwater abstractions (pumping rates of the drinking water wells were increased by 20 times in one subbasin of the catchment). Three subbasin outlets representing stream segments of different sizes were used for this evaluation. Current groundwater abstraction level had only minor impacts on the flow regime and stream biotic indices at the three subbasin outlets. The extreme abstractions, however, led to significant impacts on the small stream but had comparatively minor effects on the larger streams. The fish index responded most negatively to the groundwater abstractions, followed by the macrophyte index, decreasing, respectively, by 23.5% and 11.2% in the small stream in the extreme groundwater abstraction scenario. No apparent impact was found on macroinvertebrates in any of the three subbasin outlets. We conclude that this novel approach of a combined modelling system is a useful tool to quantitatively assess the effects of groundwater abstractions on stream biota and thereby support water planning and regulations related to groundwater abstractions. We highlight the need for developing improved biotic models that target specifically small headwater streams, which are often most affected by water abstraction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

There are infinite possible future scenarios reflecting the impacts of anthropogenic multiple stress on our planet. These impacts include changes in climate and land cover, to which aquatic ecosystems are especially vulnerable. To assess plausible developments of the future state of European surface waters, we considered two climate scenarios and three storylines describing land use, management and anthropogenic development ('Consensus', 'Techno' and 'Fragmented', which in terms of environmental protection represent best-, intermediate- and worst-case, respectively). Three lake and four river basins were selected, representing a spectrum of European conditions through a range of different human impacts and climatic, geographical and biological characteristics. Using process-based and empirical models, freshwater total nitrogen, total phosphorus and chlorophyll-a concentrations were projected for 2030 and 2060. Under current conditions, the water bodies mostly fail good ecological status. In future predictions for the Techno and Fragmented World, concentrations further increased, while concentrations generally declined for the Consensus World. Furthermore, impacts were more severe for rivers than for lakes. Main pressures identified were nutrient inputs from agriculture, land use change, inadequately managed water abstractions and climate change effects. While the basins in the Continental and Atlantic regions were primarily affected by land use changes, in the Mediterranean/Anatolian the main driver was climate change. The Boreal basins showed combined impacts of land use and climate change and clearly reflected the climate-induced future trend of agricultural activities shifting northward. The storylines showed positive effects on ecological status by classical mitigation measures in the Consensus World (e.g. riparian shading), technical improvements in the Techno World (e.g. increasing wastewater treatment efficiency) and agricultural extensification in the Fragmented World. Results emphasize the need for implementing targeted measures to reduce anthropogenic impacts and the importance of having differing levels of ambition for improving the future status of water bodies depending on the societal future to be expected., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Vegetated buffer strips (VBS) between agricultural areas and surface waters are important retention areas for eroded particulate P through which they may obtain critically high degrees of P saturation imposing high risk of soluble P leaching. We tested topsoil removal and three harvesting frequencies (once, twice, or four times per year) of natural buffer vegetation to reduce P leaching with the aim to offset erosional P accumulation and high degrees of P saturation. We used a simple numerical time-step model to estimate changes in VBS soil P levels with and without harvest. Harvesting offset erosional deposition as it resulted in an annual ammonium oxalate-extractable P reduction of 0.3 to 2.8% (25-cm topsoil content) in soils of the VBS and thus, with time, reduced potential P leaching below a baseline of 50 μg L. Topsoil removal only marginally reduced potential leaching at two sites and not anywhere near this baseline. The harvest frequency only marginally affected the annual P removal, making single annual harvests the most economical. We estimate 50 to 300 yr to reach the P leaching baseline, due to substantial amounts of P accumulated in the soils. Even in high-erosion-risk situations in our study, harvesting reduced soil P content and the P leaching risk. We suggest harvesting as a practical and efficient management to combat P leaching from agricultural VBS, not just for short-term reductions of dissolved P, but also for reductions of the total soil P pool and for possible multiple benefits for VBS., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

Objectives: The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI., Background: Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence., Methods: This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y 12 reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR., Results: A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR., Conclusions: HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Groundwater and surface water are often closely coupled and are both under the influence of multiple stressors. Stressed groundwater systems may lead to a poor ecological status of surface waters but to date no conceptual framework to analyse linked multi-stressed groundwater - surface water systems has been developed. In this paper, a framework is proposed showing the effect of groundwater on surface waters in multiple stressed systems. This framework will be illustrated by applying it to four European catchments, the Odense, Denmark, the Regge and Dinkel, Netherlands, and the Thames, UK, and by assessing its utility in analysing the propagation or buffering of multi-stressors through groundwater to surface waters in these catchments. It is shown that groundwater affects surface water flow, nutrients and temperature, and can both propagate stressors towards surface waters and buffer the effect of stressors in space and time. The effect of groundwater on drivers and states depends on catchment characteristics, stressor combinations, scale and management practises. The proposed framework shows how groundwater in lowland catchments acts as a bridge between stressors and their effects within surface waters. It shows water managers how their management areas might be influenced by groundwater, and helps them to include this important, but often overlooked part of the water cycle in their basin management plans. The analysis of the study catchments also revealed a lack of data on the temperature of both groundwater and surface water, while it is an important parameter considering future climate warming., (Copyright © 2018. Published by Elsevier B.V.)

Water pollution and water scarcity are among the main environmental challenges faced by the European Union, and multiple stressors compromise the integrity of water resources and ecosystems. Particularly in lowland areas of northern Europe, high population density, flood protection and, especially, intensive agriculture, are important drivers of water quality degradation. In addition, future climate and land use changes may interact, with uncertain consequences for water resources. Modelling approaches have become essential to address water issues and to evaluate ecosystem management. In this work, three multi-stressor future storylines combining climatic and socio-economic changes, defined at European level, have been downscaled for the Odense Fjord catchment (Denmark), giving three scenarios: High-Tech agriculture (HT), Agriculture for Nature (AN) and Market-Driven agriculture (MD). The impacts of these scenarios on water discharge and inorganic and organic nutrient loads to the streams have been simulated using the Soil and Water Assessment Tool (SWAT). The results revealed that the scenario-specific climate inputs were most important when simulating hydrology, increasing river discharge in the HT and MD scenarios (which followed the high emission 8.5 representative concentration pathway, RCP), while remaining stable in the AN scenario (RCP 4.5). Moreover, discharge was the main driver of changes in organic nutrients and inorganic phosphorus loads that consequently increased in a high emission scenario. Nevertheless, both land use (via inputs of fertilizer) and climate changes affected the nitrate transport. Different levels of fertilization yielded a decrease in the nitrate load in AN and an increase in MD. In HT, however, nitrate losses remained stable because the fertilization decrease was counteracted by a flow increase. Thus, our results suggest that N loads will ultimately depend on future land use and management in an interaction with climate changes, and this knowledge is of utmost importance for the achievement of European environmental policy goals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To explore the role of ticagrelor versus clopidogrel in coronary blood flow normalization immediately after chronic coronary total occlusion (CTO) recanalization., Background: Coronary vascular function of a CTO immediately after recanalization is demonstrated to be poor., Methods: The TIGER BVS is a prospective, double-randomized, open-label, two parallel-group controlled clinical trial to evaluate efficacy of ticagrelor versus clopidogrel in improving vascular function of coronary segment distal to CTO immediately after CTO recanalization. A total of 50 patients who receive CTO PCI will be randomized 1:1 to receive ticagrelor versus clopidogrel at least 3 days before the procedure. Immediately after CTO recanalization with Absorb BVS implantation, a specific study of vascular function under adenosine infusion will be performed. Patients will be therefore randomized 1:1 to receive angiographic follow-up with vascular function and optical coherence tomography analyses at 1- or 3-year follow-up. This study is registered on ClinicalTrials.gov with number NCT02211066., Conclusions: The TIGER BVS trial will provide the first randomized comparison between ticagrelor versus clopidogrel in recovering vascular function in CTO patients. It will also provide important data on vascular restoration therapy of Absorb BVS in this scenario., (© 2017 Wiley Periodicals, Inc.)

The SWAT model was applied to the Ompólveda River Basin (Guadalajara, central Spain) to assess the hydrological feasibility of the Pareja Limno-reservoir. A limno-reservoir is a water management infrastructure designed to counteract some negative impacts caused by large reservoirs under Mediterranean climate. Highly detailed inputs were selected to set up the model. Its performance was evaluated by graphical and statistical techniques and compared with the previous knowledge of the basin. An overall good performance was obtained during the calibration and validation periods (monthly and annual NSE values of 0.67 and 0.60, respectively, for calibration and 0.70 and 0.83, respectively, for validation). Total discharge was well simulated, and flow components prediction was acceptable. However, the model is not accurate at predicting evapotranspiration. Once evaluated, the model was used to simulate the water discharge into the Pareja Limno-reservoir during 2008 and 2009, establishing a water balance and assessing its hydrologic feasibility. The water balance predicted the absence of surplus during summer (2008 and 2009) and autumn (2009), matching up with the decrease of water level and demonstrating the usefulness of SWAT as a tool to evaluate the hydrologic feasibility of the Pareja Limno-reservoir. Very low discharges from the Ompólveda River after a sequence of normal and dry years are the main factors responsible of this phenomenon, whereas the effect of the wastewater flow redirection in the Pareja village is negligible. These results question the usefulness of the Pareja Limno-reservoir during summer, the most favorable season for recreational activities., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)