Search

The World Health Organization (WHO) and the U.S. Environmental Protection Agency (EPA) provide guidelines on the maximum levels of nitrate nitrogen (NO3-N) contained in drinking water since excess nitrate ingestion may harm human health. Thus, monitoring and controlling the NO3-N concentration is of paramount importance, especially in sources of drinking water such as the Nakdong River in South Korea. This study addresses NO3-N pollution in the Nakdong River in South Korea, where such pollution mostly comes from diffuse sources in the catchment due to the agricultural use of fertilizers. The objective of this study is to suggest guidelines for designing strategies to control NO3-N in this river using a process-based model developed with HEC-RAS. The model was built based on water quality parameters (water temperature, dissolved oxygen, ammonia nitrogen, etc.) related to NO3-N dynamics incorporating hydraulic and meteorological data. This model simulated NO3-N dynamics downstream under 55 scenarios while focusing on a section near locations of drinking water intakes. The scenarios were constructed based on variations in water quantity and quality upstream. The simulation results showed that the peak concentration of NO3-N downstream could be directly controlled by limiting the NO3-N concentration upstream. Additionally, control of the flow rate upstream could also lead to a reduction in the overall average concentration of NO3-N downstream, but this predominantly occurred when the NO3-N concentration was decreasing. In conclusion, the design and implementation of strategies for the control of NO3-N downstream should be carried out after performing a quantitative analysis of the impact of different control measures for different downstream conditions using a water quality model.

In Ecuador, 30% of the population does not consume drinking water of good quality. One of the causes is related to the deficiency in the technical skills of water operators because some have not had access to elementary, high school or higher education due to factors of extreme vulnerability. The Massive Open Online Courses (MOOCs), having an inclusive and accessible typology with attention to people at risk of social exclusion are an option to strengthen the skills of operators. Therefore, the goal of this study is to create an instructional design in MOOCs that responds to the characteristics and learning needs of a sample of 286 operators of the drinking water system. The instructional design is based on the information systems success model of DeLone and McLean and the quality principles of Merrill, Margaryan, Locke, Latham and Seijts. The results present an instructional design including quality content with objectives and learning strategies that respond to the learning characteristics of the operators as well as activities and resources with a cognitive, emotional, and behavioral didactic approach oriented at changing attitudes to learning. Finally, we can conclude that the developed instructional design promotes a more inclusive, equitable and quality education.

Increasing anthropogenic activities are affecting water quality and related ecosystem services in river basins worldwide. There is a need to identify and act on synergies between the water-energy-food (WEF) elements and the other Sustainable Development Goals (SDGs) while mediating trade-offs. The Guayas river basin (GRB), one of the major watersheds in Ecuador, is being affected by increasing urbanization, agricultural and industrial activities. In this perspective paper, we indicate the WEF interactions in the GRB linked to the SDGs. A major challenge is the geographical distance between pressures and impacts, for which environmental and agricultural governance are key to support the needed change towards sustainable development. In particular, the realization of measures to reduce the pollutant input in upstream systems will need both legislative and financial means to solve downstream water quality problems. A Bayesian belief network (BBN) framework was developed in order to support sustainable decision making in the GRB. The discussed concepts can be applied to other river basins worldwide since, in many basins, very similar food production challenges need to be addressed.

Aim This prospective longitudinal study analyses the potential role of Myocardial Work in early detection of cardiotoxicity during chemotherapy and its added value for prognosis and patients' risk stratification. Methods We enrolled 47 consecutive female patients with HER2-positive breast cancer referred for anti-cancer therapy based on anthracycline and taxane. Patients with depressed LV function at baseline were excluded. Medical therapy, clinical parameters and echocardiographic data were recorded at baseline and at 3, 6, 12 months follow-up. Additionally, cuff blood pressure was measured at the time of 2D-TTE examination and adequate echocardiographic images were stored for off-line analysis. Results CTRCD was detected in 17 patients (36%) while 30 patients remained free of CTRCD (64%). There were no intergroup differences for age, body mass index, resting heart rate and brachial arterial pressure. Both groups presented unaltered LV systolic function after 3 months follow-up yet overt cardiac dysfunction showed up in the CTRCD group at 6 months with significant decline in LVEF, GLS, MWI, MWE and CW from baseline values (LVEF, %: 56.0±4.1 vs 52.2±6.5; GLS, %: −20.9±1.9 vs −17.6±3.2; MWI, mmHg%: 2125±348 vs 1704±620; MWE, %: 95±2.6 vs 93±3.9 and CW, mmHg%: 2562±3567 vs 2212±455, p Conclusion These findings point the superiority of Myocardial Work for early type 1 CTRCD detection in comparison to the current diagnostic tools. Additionally, we suggest the add-on value of ΔWW on top of ΔGLS quantification for better patient risk stratification. These are promising results for better clinical surveillance of cardiac function during cancer treatment. Funding Acknowledgement Type of funding sources: None.

Introduction Abnormal GLS values as well as high plasma levels of NT-proBNP previous to TAVR are independent predictors for higher peri-procedural mortality. Moreover, in a subgroup of TAVR patients LV function does not recover following the procedure. Until today, it is still unclear how to predict impaired post-procedural LV function for optimal clinical patient's management. Purpose This study was set up to assess the predictive value of baseline GLS and NT-proBNP levels on LV function recovery (LVfr) in a cohort of patients with severe AS referred for TAVR. Methods A total of 25 patients (9 male, 84±5 yo, EF 50±11%) with severe AS (AVA 0.6±0.3 cm2, MPG 49±16 mmHg) referred for TAVR were included. Blood analysis and TTE were performed before intervention (baseline, bl) and at follow-up (fu). Myocardial work was analysed offline integrating the longitudinal strain and afterload pressure (SBP + AVPmean). LVfr was defined as GLS Results LV function recovered in 13 patients (52%). Despite similar EF and global MWI after TAVR, the LV contraction became more efficient as evidenced by a significant improvement (bl vs fu, p Conclusion Elevated afterload in severe AS leads to a physiological reduction of GLS. Although the decrease in afterload after TAVR beneficially affects GLS and may lead to LVfr, this was not observed in a subgroup of patients with high NT-proBNP levels in whom GLS remained impaired at follow-up. We speculate that myocardial tissue damage and fibrosis due to long lasting high pressure exposure may partly be responsible for this observation. The combination of pre-procedural NT-proBNP levels and GLS shows strong predictive potential for LVfr after TAVR and larger studies are warranted for further evaluation and cut-off values determination. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Cardiovascular Research Center Aalst (npo)

Mangroves provide multiple ecosystem services to coastal communities and their fisheries. In the Galapagos, mangroves have been primarily prized for their role as nursery grounds; though, the importance of cultural benefits, including the development of knowledge systems among fishers, needs to be further explored. Fishers’ local ecological knowledge (LEK) has been employed in the past to answer questions about the marine environment; not yet about mangroves. In such regard, this ethnoecological approach can contribute to unveil mangrove habitat-dependence relationships among fishery taxa across the life cycle, connectivity among habitats, and productivity spatial patterns across the archipelago. To access fishers’ LEK, we conducted 35 semi-structured interviews and 2 facilitated community workshops comprising 3 activities. A photo-elicitation method allowed us to extract values given to mangroves (i.e., ecosystem services), from which indirect use values were considered more relevant for fisheries. As such, the accumulation of LEK might have been crucial for the establishment of these values among fishers. By using a species-habitat association method, we revealed a high perceived connectivity between mangroves and other coastal and marine habitats in the Galapagos. Although this suggests an overall weak dependence to the ecosystem, fishers’ anecdotes allowed us to recognize novel species occurrences and exclusive habitat uses (e.g., spawning in Centropomus viridis). By applying Social Network Analysis to species-habitat association results, we learned that certain migratory commercial species (e.g., Lutjanus argentiventris, Seriola rivoliana) might constitute critical links in marine trophic webs and across seascapes. Finally, through scoring and participatory mapping methods, we revealed the prominence of western islands’ mangroves for fishery productivity, which were linked to biophysical attributes, like forest canopy and freshwater. Yet, other locations in central and southeastern islands might also be important, as they hold similar attributes. Interviews to other mangrove users (e.g., naturalist guides, park rangers, scientists; N = 33), and past scientific studies allowed us to triangulate LEK and to find complementarity among knowledge sources. Despite having an explorative focus, our work already showcases the potential of fishers’ LEK in improving mangrove research in the Galapagos, and the arising opportunities for ecosystem-based fisheries management and mangrove protection.

Simple Summary Questions on how features of aquatic invertebrates (e.g., size, feeding style, respiration mode) evolve along a gradient of flow velocity, turbidity and elevation are rarely addressed. Furthermore, another outstanding question is what is the environmental condition in which an abrupt change occurs in terms of the compositions and abundance of these organisms' features. To answer the previous questions, we collected macroinvertebrates and measured the flow velocity, turbidity and elevation in the streams of the Guayas basin (Ecuador); subsequently, we analyzed the data. We observed that the abundance of most organisms' features increased with increasing flow velocity, while they decreased with increasing turbidity. Furthermore, there was a substantial drop in the abundance of tegument-respiring invertebrates beyond the turbidity of 5 NTU and an abrupt decline in the diversity of the organisms' features below 22 m above sea level, implying the need to focus water management in these altitudinal regions. Our results suggest that there is a need to implement measures that minimize erosion to alleviate turbidity that affects these organisms. The findings of our study provide a basis to determine critical targets for aquatic ecosystem management. Although the trait concept is increasingly used in research, quantitative relations that can support in determining ecological tipping points and serve as a basis for environmental standards are lacking. This study determines changes in trait abundance along a gradient of flow velocity, turbidity and elevation, and develops trait-response curves, which facilitate the identification of ecological tipping points. Aquatic macroinvertebrates and abiotic conditions were determined at 88 different locations in the streams of the Guayas basin. After trait information collection, a set of trait diversity metrics were calculated. Negative binomial regression and linear regression were applied to relate the abundance of each trait and trait diversity metrics, respectively, to flow velocity, turbidity and elevation. Tipping points for each environmental variable in relation to traits were identified using the segmented regression method. The abundance of most traits increased with increasing velocity, while they decreased with increasing turbidity. The negative binomial regression models revealed that from a flow velocity higher than 0.5 m/s, a substantial increase in abundance occurs for several traits, and this is even more substantially noticed at values higher than 1 m/s. Furthermore, significant tipping points were also identified for elevation, wherein an abrupt decline in trait richness was observed below 22 m a.s.l., implying the need to focus water management in these altitudinal regions. Turbidity is potentially caused by erosion; thus, measures that can reduce or limit erosion within the basin should be implemented. Our findings suggest that measures mitigating the issues related to turbidity and flow velocity may lead to better aquatic ecosystem functioning. This quantitative information related to flow velocity might serve as a good basis to determine ecological flow requirements and illustrates the major impacts that hydropower dams can have in fast-running river systems. These quantitative relations between invertebrate traits and environmental conditions, as well as related tipping points, provide a basis to determine critical targets for aquatic ecosystem management, achieve improved ecosystem functioning and warrant trait diversity. This research was performed in the context of the VLIR Ecuador Biodiversity Network project. This project was funded by the Vlaamse Interuniversitaire Raad—Universitaire Ontwikkel-ingssamenwerking (VLIR-UOS), which supports partnerships between universities and university colleges in Flanders and the South.

Genera and species of Elmidae (riffle beetles) are sensitive to water pollution; however, in tropical freshwater ecosystems, their requirements regarding environmental factors need to be investigated. Species distribution models (SDMs) were established for five elmid genera in the Paute river basin (southern Ecuador) using the Random Forest (RF) algorithm considering environmental variables, i.e., meteorology, land use, hydrology, and topography. Each RF-based model was trained and optimised using cross-validation. Environmental variables that explained most of the Elmidae spatial variability were land use (i.e., riparian vegetation alteration and presence/absence of canopy), precipitation, and topography, mainly elevation and slope. The highest probability of occurrence for elmids genera was predicted in streams located within well-preserved zones. Moreover, specific ecological niches were spatially predicted for each genus. Macrelmis was predicted in the lower and forested areas, with high precipitation levels, towards the Amazon basin. Austrelmis was predicted to be in the upper parts of the basin, i.e., páramo ecosystems, with an excellent level of conservation of their riparian ecosystems. Austrolimnius and Heterelmis were also predicted in the upper parts of the basin but in more widespread elevation ranges, in the Heterelmis case, and even in some areas with a medium level of anthropisation. Neoelmis was predicted to be in the mid-region of the study basin in high altitudinal streams with a high degree of meandering. The main findings of this research are likely to contribute significantly to local conservation and restoration efforts being implemented in the study basin and could be extrapolated to similar eco-hydrological systems.

Only 35% of the Ecuadorian population consumes drinking water of “assured quality”. One of the causes is related to the deficiencies in the technical ability of the operators due to their lack of education, technical training, and experience. Massive open online courses (MOOCs) responsive to characteristics and learning needs are an option to strengthen the skills of operators. The goal of the present study is therefore to describe a methodology that includes the application of a survey and the use of statistical methods such as categorical principal component analysis (CATPCA) and cluster analysis to identify and assess learning characteristics. The results present the most frequent variables in the personal, academic, emotional, social, and cognitive aspects. They also show the preferences and learning needs of the operators. Finally, it is concluded that this study identifies common learning characteristics, needs, and preferences that are relevant for the creation of a quality personalized instructional design in MOOCs.

Recently, a wide range of models have been used in analyzing the costs and benefits of land utilization in river basins. Despite these advances, there is not enough information on how to select appropriate models to perform cost-benefit analyses. A literature search in the Web of Science (WOS) online database was implemented and resulted in the selection of 27 articles that utilized models to perform cost-benefit analyses of river basins. The models reviewed in these papers were categorized into five types: process-based, statistical, probabilistic, data-driven, and modeling frameworks or integrated models. Twenty-six models were reviewed based on their data and input variable needs and user convenience. A SWOT analysis was also performed to highlight the strengths, weaknesses, opportunities, and threats of these models. One of the main strengths is their ability to perform scenario-based analyses while the main drawback is the limited availability of data impeding the use of the models. We found that, to some extent, there is an increase in model applicability as the number of input variables increases but there are exceptions to this observation. Future studies should explicitly report on the necessary time needed for data collection, model development and/or training, and model application. This information is highly valuable to users and modelers when choosing which model to use in performing a particular cost-benefit analysis. These models can be developed and applied to assist sustainable development as well as the sustainable utilization of agricultural parcels within a river basin, which can eventually reduce the negative impacts of intensive agriculture and minimize habitat degradation on water resources.

Mangroves are unique coastal ecosystems, located in tropical and subtropical regions. Yet, the functioning of these essential ecosystems is threatened by the presence of pollutants, including pesticides originating from agricultural activities. We investigated pesticide residues in the Guayas estuarine environment, since agricultural activities rapidly increased in the Guayas river basin over the past decades. A multi-residue analysis involving a selection of 88 pesticides was performed on the white meat and the hepatopancreas of the red mangrove crab (Ucides Occidentalis) at 15 sampling sites within the Guayas estuary along with water, sediment, and leaves samples. We found that 35 active compounds were present in the Guayas estuary, of which pyrimethanil was most commonly detected and had the highest concentrations in almost all compartments. Also, cadusafos was present in all studied compartments of the Guayas mangrove system and several prohibited pesticides (including carbendazim, carbofuran, and parathion) were detected. An ecotoxicological and probabilistic consumer risk assessment pointed out that current butachlor, carbendazim, and fludioxonil concentrations can cause adverse effects in aquatic organisms in the long term. Moreover, high potential acute and chronic risks of cadusafos residues on aquatic invertebrates and of diuron on algae in the Guayas wetlands were observed. Still, the exposure results indicated that the health risk for the consumers of the commercial red mangrove crab is low concerning cadusafos, chlorpyrifos, diuron, linuron, and pyrimethanil residues in crab tissues. The findings presented in this research can provide a useful basis for local water managers and environmental conservation groups to act and reduce the usage of pesticides, to avoid threatening aquatic and human health.

Background Heart failure (HF) is a heterogenous syndrome with complex pathophysiology. Biomarkers and clinical risk scores often fail to provide optimal patient-level precision in the prognostic stratification. As utilizing single observational timepoint, they do not capture the entire care pathway with variations in individual patient management. Electronic patient records provide an opportunity to develop new artificial intelligence (AI) strategies for comprehensive prognostic re-stratification reflecting diagnostic and therapeutic management. Purpose We sought to use deep artificial intelligence (AI) and develop an unbiased predictive algorithm for all-cause mortality in a cohort of patients hospitalized with a de novo or worsened HF. Methods In a cohort of 2449 HF patients hospitalized between 2011–2017, we utilized 151 451 patient exams from 422 parameters. They included clinical phenotyping, medication, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions gathered on a routine clinical basis reflecting standard of care as captured in individual electronic records. The AI model development consisted of 101 iterations of repeated random subsampling splits into balanced training and validation sets. Results AI models yielded performance ranging from 0.83 to 0.89 AUC on the outcome-balanced validation set in predicting all-cause mortality at 30-, 90-, 180-, 360- and 720-day time-limits (Figure 1). The primary endpoint, 1-year mortality prediction model, recorded an 0.85 AUC accuracy. We observed stable model performance across all HF phenotypes: HFpEF 0.83 AUC, HFmrEF 0.85 AUC and HFrEF 0.86 AUC, respectively). Conclusion Our findings present a novel, patient-level, AI-based risk prediction of all-cause mortality in heart failure with a robust accuracy across its phenotypes. This suggests the potential of AI based predictive models in a point-of-care approach to guide clinical risk stratification. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): VZW Cardiovascular Research Center Aalst

Introduction Breast cancer patients receiving anthracyclines are particularly prone to develop cancer therapeutics-related cardiac dysfunction. Early detection of cardiotoxicity onset is required for optimal timing of cardio protection treatment. The latest guidelines consider a relative reduction of 15% in global longitudinal strain (GLS) from baseline as risk for cardiotoxicity. Nevertheless, the more recent Myocardial Work Index (MWI) offers a load-independent tool for detection of subclinical heart failure (HF). However, data in cancer patients are still scarce. Purpose This study analyses the predictive value of MWI for cardiotoxicity diagnosis after 6 months chemotherapy. Methods The study population consists of breast cancer patients referred for chemotherapy with anthracyclines and taxanes. Patients with a history of HF previous to chemotherapy or depressed LV function at baseline were excluded. Echocardiography was performed before onset of the chemotherapy (baseline) and after 6 months follow-up. LVEF, GLS and MWI were assessed offline using EchoPAC software. The values at baseline and 6 months follow-up were pairwise compared to detect subclinical cardiac dysfunction. LVEF, GLS and MWI means at baseline were taken as cut-off to compare the predictive value of each parameter. Moreover, patients were categorized in one group with GLS reduction >15% (Group 1) and one group with GLS reduction Results From April 2016 to July 2020, 28 women with breast cancer were included (age 54±11 years, LVEF 58±4%, GLS −21±2%, MWI 2160±308 mmHg). All patients underwent the same standard chemotherapy protocol (4xEC, 12xTaxol). No difference in baseline characteristics between group 1 (n=13) and group 2 (n=15) was observed. At 6 months follow up a significant decrease in LVEF (53±8%, p=0.003), GLS (−19±3%, p=0.002) and MWI (1920±391 mmHg, p=0.005) was shown without any change in blood pressure. However, while mean LVEF and GLS at baseline did not predict any significant change, patients with MWI under the mean value at baseline (n=15) presented significant lower LVEF (50±8 vs 57±6% p=0.006), GLS (−17±3 vs −20±2%, p=0.01), MWI (1733±320 vs 2136±362 mmHg, p=0.005) after 6 months. Additionally, both groups had similar MWI at baseline (2148±335 mmHg vs 2170±294 mmHg, p=0.85), whereas those patients with GLS reduction >15% showed significant lower MWI after 6 months (1694±332 mmHg vs 2116±334 mmHg, p=0.003, Figure 1). Conclusions At 6 months follow up, a decline of the LV systolic function as side effect of chemotherapy can be seen. MWI at baseline shows the best predictive value for development of cardiotoxicity, in comparison to LVEF and GLS. Further studies are warranted to better understand the role of MWI for early detection of cardiotoxicity and its clinical relevance. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Onze-Lieve-Vrouw hospital in Aalst (Belgium)

Pesticides are widely used for safeguarding agricultural yields and controlling malaria vectors, yet are simultaneously unintentionally introduced in aquatic environments. To assess the severity of this pressure in the Lake Tana Basin (Ethiopia), we evaluated the occurrence of 17 pesticide residues in the lake, tributary rivers, and associated wetlands during the wet and dry season, followed by a questionnaire. These questionnaires indicated that 35 different compounds were available in the districts surrounding the lake, including pesticides that are banned in Europe, i.e., endosulfan, dicofol, and malathion. Nevertheless, only 7 pesticide residues were detected in the assessed aquatic habitats. Of these, DDE and bifenthrin occurred most often (97.7% and 62.3%, respectively), while alachlor displayed the highest mean concentration (594 ± 468 ng/L). No significant differences were observed in residue concentrations between seasons nor between habitats. Based on an ecotoxicological risk assessment, the observed concentrations of DDE and cypermethrin pose a high risk to aquatic life, while alachlor and DDT-op residues were below the threshold values. Furthermore, a human risk assessment indicated a low risk for the population that directly consumes water from the Tana basin, while acknowledging the potential of indirect exposure through the consumption of fish and locally grown crops.

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

A 53-year-old heart transplant recipient with a past medical history of surgically treated acute type A dissection of the donor aorta 10 years following heart transplantation, presented with a Card...

Purpose Cardiac transplant-related arteriopathy remains a leading cause of morbidity and mortality in heart transplant (HTx) recipients. Recently, vessel fractional flow reserve (vFFR) derived from coronary angiography has emerged as a new diagnostic computational tool to functionally evaluate the severity of coronary artery disease (CAD). Although vFFR estimates have been shown to perform well against invasive FFR in atherosclerotic CAD, data on the use of vFFR in HTx recipients are lacking. The aim was to validate coronary angiogram-derived FFR to calculate FFR in HTx patients with and without cardiac transplant-related arteriopathy. Methods Prospective, single center study of HTx patients referred for annual check-up, undergoing surveillance coronarography. Invasive FFR was measured using a motorized device at the speed of 1.0 mm/sec in all three major coronary arteries. Angiography-derived pullback FFR was derived from the angiogram and compared with invasive FFR pullback curve. Results Overall, 13634 FFR values were extracted from the FFR pullback curves from 19 HTx patients. The mean age was 60.8 ± 9.10 years, the mean time after transplantation was 5.88 years [IQR 1.10, 12.0]. A total of 29 vessels (19 LAD, 6 LCX, 4 RCA) were analysed. Mean distal vFFR was 0.91 ± 0.05 whereas invasive distal FFR was 0.92 ± 0.07. A good correlation was found between invasive distal FFR and vFFR (r =0.635; p Conclusion In HTx patients coronary angiography-derived FFR correlates well with invasively measured wire-derived FFR. Angiography-derived FFR could be used as a novel diagnostic tool to quantify the functional severity of graft vasculopathy.

Purpose A mean pulmonary wedge pressure (mPAP) ≥ 25 mm Hg following volume load or exercise has been proposed as a partition value for detection of HfpEF. However, the hemodynamic response to volume challenge in heart transplant (Tx) recipients has never been studied. Methods 36 heart Tx recipients (Age: 65 years) with normal LV function (EF: 55 ± 7 %) and without rejection and graft vasculopathy underwent right heart catheterization to measure hemodynamic response to volume loading before and after a rapid saline infusion of 7mL/kg over 10 min. PCWP, right atrial pressure (RAP), mean pulmonary artery pressure(PA) were obtained and the PCWP and indexed(i) stroke volume(SV) data were used to construct Starling (SVindex/PCWP) curves. Pts were categorized in those with elevated filling pressures (Group DD, n=10 pts) defined by a PCWP ≥ 15 mm Hg at rest or ≥ 25 mm Hg following volume loading vs those without (Controls, n=26 pts). Results No difference in age of donor and transplant, baseline hemodynamics and EF was noted between both groups. Saline infusion significantly increased PCWP and mean PA in both Groups without any significant change in BP and heart rate. Interestingly saline infusion was associated with a significant rise in SV and SVi in Controls not in DD pts(Fig 1). Moreover, in DD pts the Starling curves revealed a larger SVi at any give PCWP compared to Controls pts. Conclusion In the transplanted heart volume loading increases filling pressures and is able to unmask left ventricular diastolic dysfunction. Interestingly, those with DD are characterized by a blunted Frank Starling response as evidenced by higher PCWP and failure to increase SV for any given PCWP. Further prospective studies are warranted to unravel the underlying mechanisms.

Introduction A pulmonary capillary wedge pressure (PCWP) ≥25 mm Hg following volume load or exercise has been proposed as a partition value for detection of HfpEF. However, the hemodynamic response to volume challenge in heart transplant (Tx) recipients has never been studied. Methods 24 heart Tx recipients (age: 65 years) with normal LV function (55±7%) and without rejection and graft vasculopathy underwent right heart catheterization to measure hemodynamic response to volume loading before and after a rapid saline infusion of 7mL/kg over 10 min. PCWP, right atrial pressure (RAP), mean pulmonary artery pressure (AP) were obtained and the PCWP and indexed (i) stroke volume (SV) data were used to construct Starling (SVindex/PCWP) curves. Pts were categorized in those with elevated filling pressures (Group A, n=13 pts) defined by a PCWP ≥15 mm Hg at rest or ≥25 mm Hg following volume loading vs those without (Group B, n=11 pts). Results No difference in age of donor and transplant heart, baseline hemodynamics and EF was noted between both groups. Saline infusion significantly increased PCWP and mean AP in both Groups (table 1) without any significant change in BP and heart rate. Interestingly saline infusion was associated with a significant rise in SV and SVi in Group B not in Group A pts. Moreover, in Group B pts the Starling curves revealed a larger SVi at any give PCWP compared to Group A pts (Fig.1). Table 1 All (n=24) Group A (n=13) Group B (n=11) Baseline Volume Loading Baseline Volume Loading Baseline Volume Loading RAP (mm Hg) 5.3±4.1 9.2±4.8* 7.6±4.8 11.4±5.2* 3.8±2.5 7.3±1.9* Mean AP 18.4±5.4 24.1±5.9* 21.7±5.1 26.8±6.5** 14.9±2.4 20.8±2.6* PCWP 12.1±4.9 16.8±6.7* 15.0±4.9 19.8±6.5** 8.4±1.9 14.6±3.7* SV 71.4±19.6 72.5±23.6 73.2±6.2 72.4±6.2 69.2±14.6 79.2±3.9 SViml/m2) 37.4±9.2 37.9±11.2 36.7±7.1 38.7±9.9 35.3±6.0 40.5±5.2* *p Figure 1 Conclusions In the transplanted heart volume loading increases filling pressures and is able to unmask left ventricular diastolic dysfunction. Interestingly, those with HFpEF are characterized by a blunted Frank Starling response as evidenced by higher PCWP and failure to increase SV for any given PCWP. Further prospective studies are warranted to unravel the underlying mechanisms.

Diuretic resistance in acute heart failure is a common clinical problem, and it is associated with adverse outcomes. Effective therapies are still lacking. The Doraya catheter, a temporary intravenous flow regulator placed in the inferior vena cava below the level of the renal veins, is a novel device designed to target renal and cardiac congestion, thereby improving diuretic response. A first-in-man clinical study is currently ongoing.

Huge efforts have been made during the past decades to improve the water quality and to restore the physical habitat of rivers and streams in western Europe. This has led to an improvement in biological water quality and an increase in fish stocks in many countries. However, several rheophilic fish species such as brown trout are still categorized as vulnerable in lowland streams in Flanders (Belgium). In order to support cost‐efficient restoration programs, habitat suitability modeling can be used. In this study, we developed an ensemble of habitat suitability models using metaheuristic algorithms to explore the importance of a large number of environmental variables, including chemical, physical, and hydromorphological characteristics to determine the suitable habitat for reintroduction of brown trout in the Zwalm River basin (Flanders, Belgium), which is included in the Habitats Directive. Mean stream velocity, water temperature, hiding opportunities, and presence of pools or riffles were identified as the most important variables determining the habitat suitability. Brown trout mainly preferred streams with a relatively high mean reach stream velocity (0.2–1 m/s), a low water temperature (7–15°C), and the presence of pools. The ensemble of models indicated that most of the tributaries and headwaters were suitable for the species. Synthesis and applications. Our results indicate that this modeling approach can be used to support river management, not only for brown trout but also for other species in similar geographical regions. Specifically for the Zwalm River basin, future restoration of the physical habitat, removal of the remaining migration barriers and the development of suitable spawning grounds could promote the successful restoration of brown trout.

The brand new 2016 ESC guidelines for the treatment of acute and chronic heart failure continue to give a prominent place to mineralocorticoid receptor antagonists in the treatment of chronic heart failure with reduced ejection fraction (HFrEF). In the prevention of HF hospitalization and death, a class I, level of recommendation A, is given to MRAs for patients with HFrEF, who remain symptomatic despite treatment with an ACE-inhibitor and a beta-blocker and have an LVEF below 35 %. This recommendation is primarily based on two landmark trials, the RALES trial (for spironolactone) and the EMPHASIS-HF trial (for eplerenone). A crucial question is, however, why MRAs are advised only in “third place,” i.e., after optimal up-titration of ACE-inhibitors and beta-blockers. We wonder whether MRAs could not or should not be given earlier in the treatment of HFrEF, namely before or together with the up-titration of ACE-inhibitors and beta-blockers. Several arguments to support this plea are described in this short paper.

Objective Atrial fibrillation (AF) is a common arrhythmia in clinical practice. AF fulfils many of the criteria for a screening programme. No data about the prevalence of AF in non-hospitalized patients are available in Belgium. The aim of the study was to assess feasibility and effectiveness of a nationwide-organized voluntary screening programme in the general population in Belgium. Methods A total of 13.564 participants were screened, of whom 10,758 were older than 40 years (GSP group). Participants filled in stroke risk stratification questionnaires (CHADS2 and CHA2DS2-VASc). A one-lead electrocardiogram was performed. Results 228 participants had AF at the time of screening (AF group), with 125 women and 103 men (i.e. 1.9% and 2.6% of total women and men), representing a prevalence of 2.2% (95% Cl 1.3% and 3.0%) of the screened population. Age of the AF group was 67 +/- 12 y (range 40-87 y). Using the CHADS2-score, 58% of participants with a positive AF screening had a high risk score, and 21% had an intermediate risk score. Using the CHA2DS2-VASc-score, 72% of the participants had a high risk score, and 21% had an intermediate risk score. Conclusion AF was present in 2.2% of the respondents. At least 60% of AF group had an increased risk for thrombo-embolism. Although substantial methodological issues limit the exact interpretation of these results, the present study shows that a volunatry screening programme with a simple screening protocol is able to detect an important number of patients with previously undetected AF.

Two rock avalanches in Troms County – the Grotlandsura and Russenes – were selected as CRONUS-EU natural cosmogenic 10Be production-rate calibration sites because they (a) preserve large boulders that have been continuously exposed to cosmic irradiation since their emplacement; (b) contain boulders with abundant quartz phenocrysts and veins with low concentrations of naturally-occurring 9Be (typically < 1.5 ppb); and (c) have reliable minimum radiocarbon ages of 11,424 ± 108 cal yr BP and 10,942 ± 77 cal yr BP (1σ), respectively. Quartz samples (n = 6) from these two sites contained between 4.28 × 104 and 5.06 × 104 at 10Be/g using the 1.387 Myr 10Be half-life. Determination of these concentrations accounts for topographic and self-shielding, and effects on nuclide production due to isostatic rebound are shown to be negligible. Persistent, constant snow and moss cover cannot be proven, but if taken into consideration they may have reduced 10Be concentrations by 10%. Using the 10Be half-life of 1.387 Myr and the Stone scaling scheme, and accounting for snow- and moss-cover, we calculate an error-weighted mean total 10Be production rate of 4.12 ± 0.19 at/g/yr (1σ). A corresponding error-weighted mean spallogenic 10Be production rate is 3.96 ± 0.16 at/g/yr (1σ), respectively. These are in agreement within uncertainty with other 10Be production rates in the literature, but are significantly, statistically lower than the global average 10Be production rate. This research indicates, like other recent studies, that the production of cosmogenic 10Be in quartz is lower than previously established by other production-rate calibration projects. Similarly, our findings indicate that regional cosmogenic production rates should be used for determining exposure ages of landforms in order to increase the accuracy of those ages. As such, using the total 10Be production rate from our study, we determine an error-weighted mean surface-exposure age of a third rock avalanche in Troms County (the Holen avalanche) to be 7.5 ± 0.3 kyr (1σ). This age suggests that the rock avalanche occurred shortly after the 8.2 kyr cooling event, just as the radiocarbon ages of the Grotlandsura and Russenes avalanches confirm field evidence that those rock-slope failures occurred shortly after deglaciation.

The confidence in surface exposure dating and related research, such as erosion rate studies or burial dating, strongly depends on the accuracy and precision of the currently used production rates of in situ-produced cosmogenic nuclides. Reducing the uncertainties of nuclide production rates by more accurate calibrations with independently dated natural rock surfaces is crucial for further improving the quantification of earth surface processes. Here we use surface samples from the 760 ± 2 ka old Bishop Tuff in eastern California to quantify the 10 Be/ 21 Ne and 26 Al/ 21 Ne production rate ratios in quartz. Our determination is based on (1) measured nuclide concentrations of cosmogenic 10 Be, 21 Ne, and 26 Al, (2) a conservative estimate for the erosion of the tuff in the Volcanic Tableland area, which we base on our previously published 21 Ne concentrations [Goethals, M.M., Niedermann, S., Hetzel, R., Fenton, C.R., 2009. Determining the impact of faulting on the rate of erosion in a low-relief landscape: A case study using in situ produced 21 Ne on active normal faults in the Bishop Tuff, California. Geomorphology 103, 401–413] and a conservative estimate for the uncertainty of the 21 Ne production rate, and (3) the assumption of steady-state erosion. Other assumptions, such as the applied scaling procedure, the muon contribution to nuclide production, or the attenuation lengths of neutrons and muons in rock, do not substantially affect the results. Based on 13 samples, the following average production rate ratios and conservative uncertainty estimates are obtained for sea level, high latitude, open sky, and rock surface: 0.249 ± 0.009 or 0.232 ± 0.009 for 10 Be/ 21 Ne using 10 Be half-lives of 1.51 and 1.39 Ma, respectively, and 1.80 ± 0.09 for 26 Al/ 21 Ne (for an 26 Al half-life of 0.72 Ma). The 10 Be/ 21 Ne and the 26 Al/ 21 Ne production ratios are consistent with currently used production rates but the ratios are much more precise than previous determinations. The resulting 26 Al/ 10 Be production ratio of 7.23 ± 0.45 (for a 10 Be half-life of 1.51 Ma) or 7.76 ± 0.49 (for a 10 Be half-life of 1.39 Ma) is high when compared to previously published values. We discuss reasons for this difference, amongst them the possibility that 26 Al analyses in general might be compromised by artefacts affecting the stable Al concentration measurements. When combined with a 10 Be production rate of 5.01 at g − 1 a − 1 for the 1.51 Ma half-life (or 4.61 at g − 1 a − 1 for the 1.39 Ma half-life), our production ratios convert to 21 Ne and 26 Al production rates of 20.1 and 36.2 at g − 1 a − 1 (or 19.9 and 35.7 at g − 1 a − 1 ), respectively.

Salmon calcitonin, CT(1-32).NH2, was synthesised by the trypsin-mediated coupling of the peptide fragments CT(1-24) and CT(25-32).NH2, prepared by conventional Fmoc solid-phase chemistry. Optimal conditions regarding reaction time course, pH, proportion of catalyst, substrate concentration and composition of the reaction medium were determined from initial studies on the coupling of CT(1-11) to CT(12-24) and of CT(12-24) to CT(25-32).NH2. For the final successful semisynthesis, we found that it was unnecessary to protect lysine residues not involved in the coupling, and that secondary hydrolysis at these sites could be prevented by increasing the pH of the reaction medium. The reaction achieved equilibrium after 30-45 min, with overall conversion of around 30% of the initial amount of CT(1-24) substrate into product. Yields were depressed due to cyclisation of the CT(1-24) substrate via air-oxidation of the Cys1 and Cys7 residues.

Gelsolin is an actin-binding protein (82 kDa) consisting of six repeated segments (S1-S6), each approximately 120 residues long. It interacts with phospholipids and we previously showed that phosphatidylinositol 4,5-bisphosphate promotes phosphorylation of gelsolin by the tyrosine kinase c-Src. We used a combination of different methods, such as thin-layer chromatography and anti-phosphotyrosine-agarose immunoprecipitation of phosphopeptides combined with matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) and post source decay (PSD) analysis, to identify the phosphorylation sites in gelsolin. The major phosphorylation site (Tyr438) was located in subdomain 4 (S4). Phosphorylation of gelsolin in the gelsolin-actin2 complex was inhibited by 90%. Gelsolin phosphorylation by c-Src in the presence of lysophosphatidic acid also revealed Tyr438 as the most prominent site. Additional minor sites were found using the anti-phosphotyrosine bead immunoprecipitation method followed by MALDI-MS and PSD analysis. These sites, representing approximately 5% of the total phosphate incorporation, were identified as Tyr59, Tyr382, Tyr576, and Tyr624. Based on these results we generated antibodies which specifically recognize Tyr438 phosphorylated gelsolin.