Development of the Environmental Model for Population Annoyance and Risk Analysis. Partial validation and sensitivity analysis

In this report details on, and background to a study on the extent and effects of exposure to noise from road, rail and air traffic in the framework of the fifth National Environmental Outlook are given as they are expected to develop from 1995 to 2030. The results have indicated environmental noise to be among the persistent environmental problems in the Netherlands. The whole process, from the basic data collection and processing to the application of a computer model for noise mapping and the analysis of its results has been described. The most comprehensive description is dedicated to the starting points and assumptions in line with the methodological approach. Special focus has also been placed on the way the effects of existing policy and measures to reduce noise (annoyance) in the Netherlands ar estimated and taken into account. The reproducibility of the figures and conclusions given in this fifth Environmental Outlook have been adequately handled in this way, while providing the interested reader with all the necessary background information.Aan de hand van de modelvergelijking, validatie en gevoeligheidsanalyse is getracht de onzekerheden in de modeluitkomsten van het Landelijke Beeld van Verstoring (EMPARA) te kwantificeren. De belangrijkste bevinding is dat de nauwkeurigheid van de 'gemiddelde' geluidbelasting berekend op een gebied, minimaal ter grootte van een middelgrote stad, zo'n 2 decibel bedraagt. De nauwkeurigheid kan worden vertaald in een onzekerheid in de geaggregeerde modelresultaten (geluidbelast oppervlak, geluidbelaste woningen) van enkele tientallen procenten. Een uitzondering vormt het aantal hoogbelaste woningen (>65 dB). Bij dit aantal moet in sommige situaties rekening worden gehouden met een onzekerheid die gelijk is aan het berekende aantal. De onzekerheden in de trends zijn over het algemeen kleiner. Op basis van de bevindingen is geconcludeerd dat het model geschikt is om op landelijke schaal evaluaties uit te voeren van scenario's en het uitvoeren van beleid, zoals dat bijvoorbeeld gebeurt in het kader van de Milieuverkenningen. Voor het jaarlijkse, op landelijke schaal monitoren van (kleine) veranderingen, en zeker voor studies aan specifieke maatregelen en lokale situaties is het model over het algemeen te onnauwkeurig

Development of the Environmental Model for Population Annoyance and Risk Analysis. Partial validation and sensitivity analysis

Aan de hand van de modelvergelijking, validatie en gevoeligheidsanalyse is getracht de onzekerheden in de modeluitkomsten van het Landelijke Beeld van Verstoring (EMPARA) te kwantificeren. De belangrijkste bevinding is dat de nauwkeurigheid van de 'gemiddelde' geluidbelasting berekend op een gebied, minimaal ter grootte van een middelgrote stad, zo'n 2 decibel bedraagt. De nauwkeurigheid kan worden vertaald in een onzekerheid in de geaggregeerde modelresultaten (geluidbelast oppervlak, geluidbelaste woningen) van enkele tientallen procenten. Een uitzondering vormt het aantal hoogbelaste woningen (>65 dB). Bij dit aantal moet in sommige situaties rekening worden gehouden met een onzekerheid die gelijk is aan het berekende aantal. De onzekerheden in de trends zijn over het algemeen kleiner. Op basis van de bevindingen is geconcludeerd dat het model geschikt is om op landelijke schaal evaluaties uit te voeren van scenario's en het uitvoeren van beleid, zoals dat bijvoorbeeld gebeurt in het kader van de Milieuverkenningen. Voor het jaarlijkse, op landelijke schaal monitoren van (kleine) veranderingen, en zeker voor studies aan specifieke maatregelen en lokale situaties is het model over het algemeen te onnauwkeurig.In this report details on, and background to a study on the extent and effects of exposure to noise from road, rail and air traffic in the framework of the fifth National Environmental Outlook are given as they are expected to develop from 1995 to 2030. The results have indicated environmental noise to be among the persistent environmental problems in the Netherlands. The whole process, from the basic data collection and processing to the application of a computer model for noise mapping and the analysis of its results has been described. The most comprehensive description is dedicated to the starting points and assumptions in line with the methodological approach. Special focus has also been placed on the way the effects of existing policy and measures to reduce noise (annoyance) in the Netherlands ar estimated and taken into account. The reproducibility of the figures and conclusions given in this fifth Environmental Outlook have been adequately handled in this way, while providing the interested reader with all the necessary background information.DGM-S&

The stereoisomers of 17α-[123I]iodovinyloestradiol and its 11α-methoxy derivative evaluated for their oestrogen receptor binding in human MCF-7 cells and rat uterus, and their distribution in immature rats

We studied the potential of both stereoisomers of 17-[123I]iodovinyloestradiol (E- andZ-[123I]IVE) and of 11-methoxy-17-[123I]iodovinyloestradiol (E-andZ-[123I]MIVE) as suitable radioligands for the imaging of oestrogen receptor(ER)-positive human breast tumours. The 17-[123I]iodovinyloestradiols were prepared stereospecifically by oxidative radio-iododestannylation of the corresponding 17-tri-n-butylstannylvi-nyloestradiol precursors. Competitive binding studies were performed in order to determine the relative binding affinity (RBA) of the unlabelled 17-iodovinyloes-tradiols for the ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their123I-labelled analogues were studied in immature female rats. All four 17-iodovi-nyloestradiols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreasing potency: RBA of DES >Z-IVE >Z-MIVE >E-MIVE E-IVE. Neither of these 17-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasma. The biodistribution studies showed ER-mediated uptake in the uterus, ovaries and pituitary, that ofE- andZ-[123I]MIVE being higher than that ofE- andZ-[123I]IVE. High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24 h), were exhibited by both isomers of [123I]MIVE. The uterus-to-blood uptake ratio was higher forE-[123I]MIVE. However, the uterus-to-fat uptake ratio appeared to be higher for theZ-isomer of [123I]MIVE, especially at 24 h after injection. Metabolic properties and temperature effects, which play a more important role in vivo, probably cause the discrepancies seen between in vitro and in vivo binding results. On the basis of their in vitro binding properties and in vivo distribution characteristics we conclude thatE- andZ-[123I]MIVE could be suitable radioligands for the diagnostic imaging of ER in human breast cancer. Therefore, further studies with these radioligands in mature normal and tumour-bearing rats are warranted

Clinical presentation, disease course, and outcome of COVID-19 in hospitalized patients with and without pre-existing cardiac disease : a cohort study across 18 countries

AIMS: Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. METHODS AND RESULTS: We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66-75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02-1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10-1.30; P < 0.018) particularly for severe (New York Heart Association class III/IV) heart failure (aRR 1.41, 95% CI 1.20-1.64; P < 0.018). None of the other heart disease subtypes, including ischaemic heart disease, remained significant after multivariable adjustment. Serious cardiac complications were diagnosed in <1% of patients. CONCLUSION: Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization

Clinical presentation, disease course, and outcome of COVID-19 in hospitalized patients with and without pre-existing cardiac disease: a cohort study across 18 countries

AIMS: Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. METHODS AND RESULTS: We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66-75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02-1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10-1.30; P < 0.018) particularly for severe (New York Heart Association class III/IV) heart failure (aRR 1.41, 95% CI 1.20-1.64; P < 0.018). None of the other heart disease subtypes, including ischaemic heart disease, remained significant after multivariable adjustment. Serious cardiac complications were diagnosed in <1% of patients. CONCLUSION: Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization