ENDIS-RISKS: endocrine disruption in the Scheldt estuary - a field study

ENDIS-RISKS, a multidisciplinary research project with five institutes, evaluates the distribution, exposure and effects of endocrine disruptors in the Scheldt Estuary. This estuary is known to be one of the most polluted estuaries in the world. Untreated domestic wastewater and effluents of the industrial areas of Ghent and Antwerp are to a large extent responsible for this pollution. During an intensive field study of four years, eight sampling campaigns were executed on seven sampling points along the Scheldt Estuary. A detailed analysis of the distribution of endocrine disrupting substances in the Scheldt Estuary was executed. Water, sediment, suspended solids and biota were analysed for seven groups of chemicals: estrogens, pesticides, organotins, polyaromatic components, polyaromatic hydrocarbons and phenols. Special attention was given to the estuarine mysid shrimp Neomysis integer. Its ecotoxicology and population characteristics were studied in detail. A selection of results of this field study is put forward. Water samples, tested in vitro for their potential to bind with estrogen, revealed more estrogenic activity in the more upstream stations. Concentrations of chlorotriazine herbicides in water samples, were higher in the upstream reaches compared to the downstream sites. Analyses of TBT in mysid shrimps revealed high concentrations (>2mg.kg-1 dry weight) which suggests a high bioaccumulation capacity. Population characteristics results of N. integer show that it has a broader distribution range, with a shift more upstream, in comparison with historical data (Mees et al., 1995). On the other hand, length distribution of developmental stages of N. integer along the estuary indicates some environmental stress, caused by the estuarine gradient or by pollutants. Some hypotheses will be put forward to explain these patterns

Assessing cycling-friendly environments for children: are micro-environmental factors equally important across different street settings?

BACKGROUND: As physical activity levels decrease as children age, sustainable and accessible forms of physical activity are needed from a young age. Transportation cycling is one such physical activity and has been associated with many benefits. The aims of the study were to identify whether manipulating micro-environmental factors (e.g. speed limis, evenness of cycle path) within a photographed street influences the perceived supportiveness for transportation cycling; and whether changing these micro-environmental factors has the same effect across different street settings. METHODS: We recruited 305 fifth and sixth grade children and their parents from twelve randomly selected primary schools in Flanders, Belgium. They completed a web-based questionnaire including 12 choice-based conjoint tasks, in which they had to choose between two possible routes depicted on manipulated photographs, which the child would cycle along. The routes differed in four attributes: general street setting (enclosed, half open, open), evenness of cycle path (very uneven, moderately uneven, even), speed limit (70 km/h, 50 km/h, 30 km/h) and degree of separation between a cycle path and motorised traffic (no separation, curb, hedge). Hierarchical Bayes analyses revealed the relative importance of each micro-environmental attribute across the three street settings. RESULTS: For each attribute, children and their parents chose routes that had the best alternative (i.e. open street setting, even cycle path, 30 km/h, a hedge separating the cycle path from motorised traffic). The evenness of the cycle path and lower speed limit had the largest effect for the children, while the degree of separation and lower speed limit had the largest effect for their parents. Interactions between micro-scale and macro-scale factors revealed differences in the magnitude but not direction of their effects on route choice. The results held across the different kinds of street settings tested. CONCLUSIONS: Improving micro-scale attributes may increase the supportiveness of a street for children\u27s transportation cycling. We call for on-site research to test effects of changes in micro-environmental attributes on transportation cycling among children

Endocrine disruption in the Scheldt estuary distribution, exposure and effects (ENDIS-RISKS). Final report

ENDIS-RISKS is a multidisciplinary, research project conducted by five institutes. This project aimed to assess the distribution, exposure and effects of endocrine disruptors in the Scheldt estuary, with specific attention to invertebrates. The Scheldt estuary is known to be one of the most polluted estuaries in the world. The industrial areas of Ghent and Antwerp are to a large extent responsible for this pollution. To achieve these goals detailed knowledge of the distribution and long-term effects of these substances is needed. This information is crucial for the development of future-oriented policy measures at the national and European level. The project can be divided into four different research phases. In Phase I the occurance and distribution of endocrine disrupting substances in the Scheldt estuary was studied. Water, sediment, suspended solids and biota were sampled 3 times a year for a period of 4 years (2002-2006). In all these matrices, 7 groups of chemicals were analysed: estrogens, pesticides, phthalates, organotins, polyaromatic components (PCBs, PBDEs), polyaromatic hydrocarbons (PAHs) and phenols. All the analyzed chemicals are on the OSPAR list of priority chemicals or are indicated as endocrine disruptors on this list. The different water samples were also tested using in vitro assays to assess their potential to bind to the (human) estrogen and androgen receptor. Phase II evaluated the exposure of biota occuring in the Scheldt estuary to endocrine disrupting substances. Based on the results of the chemical analysis, priority substances were selected. Phase III studied the effects of endocrine disrupting substances occurring in the Scheldt estuary on resident mysid shrimp populations (laboratory and field studies). Substances of concern were selected and tested in the laboratory to evaluate their effects on the estuarine mysid Neomysis integer. In the context of this project, three new assays using invertebrate-specific endpoints were developed to examine the effect of endocrine disrupting chemicals (EDCs) on molting, embryogenesis and vitellogenesis of N. integer. Finally, in Phase IV laboratory and field results were used to perform a preliminary environmental risk assessment of endocrine disruptors in the Scheldt estuary. Samples were collected along the salinity gradiënt of the Scheldt estuary with the RV Belgica. Water samples were taken with Teflon-coated Go-Flo bottles (10L), sediment samples with Van Veen Grab, biota with a hyperbentic sledge, and suspended particulate matter (SPM) was continuously sampled with an Alfa Laval flow-through centrifuge. For the chemical analysis, protocols were developed to analyse estrogens, organotriazine herbicides, organochlorine pesticides, phtalates, organotins, PAHs, PCBs, and PBDEs in the different matrices: i.e. water, sediment, SPM and biota.Experimental studies were performed to analyse growth, molting, embryogenesis and vitellogenesis of N. integer. These studies were needed to develop ecotoxicological assays to evaluate EDCs on these physiological processes. To study growth of N. integer, organisms were individually transferrred in exposure solutions and molts were collected to measure the growth after each molting. To study embryogenesis, embryos were taking out of the marsupium and placed in multiwell plates. Each day survival, developmental stages and hatching was analysed. To study vitellogenesis, vitellin was isolated from eggs with gelfitration and polyclonal antibodies were developed (in rabbits). With the isolated vitellin and the antibodies an enzyme-linked immunosorbent assay (ELISA) was developed. Vitellin was quatified in ovigerous females exposed to test compound in the laboratory and in females collected from the different sampling sites of the Scheldt estuary. In addition to vitellin levels, energy allocation and testosterone metabolism was examined in field collected mysids. Finally, results from population stu

Mysid crustaceans as standard models for the screening and testing of endocrine-disrupting chemicals

Author Posting. © Springer, 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 205-219, doi:10.1007/s10646-006-0122-0.Investigative efforts into the potential endocrine-disrupting effects of chemicals have mainly concentrated on vertebrates, with significantly less attention paid to understanding potential endocrine disruption in the invertebrates. Given that invertebrates account for at least 95% of all known animal species and are critical to ecosystem structure and function, it remains essential to close this gap in knowledge and research. The lack of progress regarding endocrine disruption in invertebrates is still largely due to: (1) our ignorance of mode-of-action, physiological control, and hormone structure and function in invertebrates; (2) lack of a standardized invertebrate assay; (3) the irrelevance to most invertebrates of the proposed activity-based biological indicators for endocrine disruptor exposure (androgen, estrogen and thyroid); (4) limited field studies. Past and ongoing research efforts using the standard invertebrate toxicity test model, the mysid shrimp, have aimed at addressing some of these issues. The present review serves as an update to a previous publication on the use of mysid shrimp for the evaluation of endocrine disruptors (Verslycke et al., 2004a). It summarizes recent investigative efforts that have significantly advanced our understanding of invertebrate-specific endocrine toxicity, population modeling, field studies, and transgeneration standard test development using the mysid model.Supported by a Fellowship of the Belgian American Educational Foundation

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362