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Endpoint sensitivity in Amphibian Metamorphosis Assay.(2019-01-15)The Amphibian Metamorphosis Assay (AMA) is a screening test for detecting chemicals with thyroid activity. There is little experience in data interpretation and in using AMA data for screening, testing and identifying endocrine disruptors. To investigate the sensitivity of different endpoints of the AMA, the publically available data for 57 thyroid active and inactive chemicals were compiled and analyzed. Endpoints body weight and length appeared as sensitive as apical thyroid responsive endpoints hind limb length (HLL) and developmental stage (DS) for 12 thyroid active chemicals. The sensitivity of body weight, length and HLL was comparable, which is higher than that of DS for 45 thyroid inactive chemicals. The decision logic of the AMA suggests that an advanced development alone indicates thyroid activity. The analysis here showed that advanced development at day 7 could indicate thyroid activity of a chemical. However, advanced development at day 21 may be influenced by thyroid inactive chemicals. Among 39 thyroid inactive chemicals, which affected one or more endpoints, 33% and 77% induced changes in HLL and/or DS at day 7 and 21, respectively; only 10% influenced thyroid histology. These results showed that apical thyroid responsive endpoints HLL and DS are influenced by thyroid active chemicals as well as thyroid inactive chemical. Both endpoints should be combined with thyroid histology for the identification of thyroid active chemicals. The use of the AMA in a testing strategy to identify chemicals with thyroid activity is discussed.
Fast approximate computation of cervical cancer screening outcomes by a deterministic multiple-type HPV progression model.(2019-01-16)Cervical cancer arises differentially from infections with up to 14 high-risk human papillomavirus (HPV) types, making model-based evaluations of cervical cancer screening strategies computationally heavy and structurally complex. Thus, with the high number of HPV types, microsimulation is typically used to investigate cervical cancer screening strategies. We developed a feasible deterministic model that integrates varying natural history of cervical cancer by the different high-risk HPV types with compressed mixture representations of the screened population, allowing for fast computation of screening interventions. To evaluate the method, we built a corresponding microsimulation model. The outcomes of the deterministic model were stable over different levels of compression and agreed with the microsimulation model for all disease states, screening outcomes, and levels of cancer incidence. The compression reduced the computation time more than 1000 fold when compared to microsimulation in a cohort of 1 million women. The compressed mixture representations enable the assessment of uncertainties surrounding the natural history of cervical cancer and screening decisions in a computationally undemanding way.
Why are the public so positive about colorectal cancer screening?(2018-10-30)Colorectal cancer (CRC) screening is widely recommended. Earlier research showed that the general public are positive about CRC screening, as too the eligible CRC screening population. Among the eligible CRC screening population this positive perception has been shown to be associated with their perceptions of cancer, preventive health screening and their own health. It is unclear whether these concepts are also associated with the positive perception of the general public. Knowing this can provide insight into the context in which public perception concerning CRC screening is established. The aim of our study was to examine which main perceptions are associated with the public perception concerning CRC screening. An online survey was carried out in a Dutch population sample (adults 18+) among 1679 respondents (response rate was 56%). We assessed the public's perceptions concerning cancer, preventive health screening, own health, and the government, and examined their possible association with public opinion concerning CRC screening. The public's positive attitude towards CRC screening is associated with the public's positive attitude towards preventive health screening in general, their perceived seriousness of cancer, their belief of health being important, and their trust in the government regarding national screening programmes. Trust in the government and perceptions regarding the seriousness of cancer, preventive health screening and the importance of one's health seem to be important factors influencing how the public view CRC screening. The public are likely to process information about CRC screening in such a way that it confirms their existing beliefs of cancer being serious and preventive screening being positive. This makes it likely that they will notice information about the possible benefits of CRC screening more than information about its possible downsides, which would also contribute to the positive perception of CRC screening.