Bahar, Rumana; Hartmann, Claudia H; Rodriguez, Karl A; Denny, Ashley D; Busuttil, Rita A; Dollé, Martijn E T; Calder, R Brent; Chisholm, Gary B; Pollock, Brad H; Klein, Christoph A; Vijg, Jan(2006-06-22)
The accumulation of somatic DNA damage has been implicated as a cause of ageing in metazoa. One possible mechanism by which increased DNA damage could lead to cellular degeneration and death is by stochastic deregulation of gene expression. Here we directly test for increased transcriptional noise in aged tissue by dissociating single cardiomyocytes from fresh heart samples of both young and old mice, followed by global mRNA amplification and quantification of mRNA levels in a panel of housekeeping and heart-specific genes. Although gene expression levels already varied among cardiomyocytes from young heart, this heterogeneity was significantly elevated at old age. We had demonstrated previously an increased load of genome rearrangements and other mutations in the heart of aged mice. To confirm that increased stochasticity of gene expression could be a result of increased genome damage, we treated mouse embryonic fibroblasts in culture with hydrogen peroxide. Such treatment resulted in a significant increase in cell-to-cell variation in gene expression, which was found to parallel the induction and persistence of genome rearrangement mutations at a lacZ reporter locus. These results underscore the stochastic nature of the ageing process, and could provide a mechanism for age-related cellular degeneration and death in tissues of multicellular organisms.
Amsterdam, J G C van; Best, W; Opperhuizen, A; Wolff, F A de(2004-02-01)
The assessment procedure of new synthetic illicit drugs that are not documented in the UN treaty on psychotropic drugs was evaluated using a modified Electre model. Drugs were evaluated by an expert panel via the open Delphi approach, where the written score was discussed on 16 items, covering medical, health, legal, and criminalistic issues of the drugs. After this face-to-face discussion the drugs were scored again. Taking the assessment of ketamine as an example, it appeared that each expert used its own scale to score, and that policymakers do not score deviant from experts trained in the medical-biological field. Of the five drugs evaluated by the panel, p-methoxy-metamphetamine (PMMA), gamma-hydroxybutyric acid (GHB), and 4-methylthio-amphetamine (MTA) were assessed as more adverse than ketamine and psilocine and psilocybine-containing mushrooms. Whereas some experts slightly adjusted during the assessment procedure their opinion on ketamine and PMMA, the opinion on mushrooms was not affected by the discussion held between the two scoring rounds. All experts rank the five drugs in a similar way on the adverse effect scale i.e., concordance scale of the Electre model, indicating unanimity in the expert panel with respect to the risk classification of these abused drugs.
Grievink, Linda; Velden, Peter G van der; Yzermans, C Joris; Roorda, Jan; Stellato, Rebecca K(2006-10-01)
PURPOSE: The aim was to study selective participation and its effect on prevalence estimates in a health survey of affected residents 3 weeks after a man-made disaster in The Netherlands (May 13, 2000). METHODS: All affected adult residents were invited to participate. Survey (questionnaire) data were combined with electronic medical records of residents' general practitioners (GPs). Data for demographics, relocation, utilization, and morbidity 1 year predisaster and 1 year postdisaster were used. RESULTS: The survey participation rate was 26% (N = 1171). Women (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.28-1.67), those living with a partner (OR, 2.00; 95% CI, 1.72-2.33), those aged 45 to 64 years (OR, 2.00; 95% CI, 1.59-2.52), and immigrants (OR, 1.50; 95% CI, 1.30-1.74) were more likely to participate. Participation rate was not affected by relocation because of the disaster. Participants in the survey consulted their GPs for health problems in the year before and after the disaster more often than nonparticipants. Although there was selective participation, multiple imputation barely affected prevalence estimates of health problems in the survey 3 weeks postdisaster. CONCLUSIONS: Estimating actual selection bias in disaster studies gives better information about the study representativeness. This is important for policy making and providing effective health care.
Cooke, Roger M; Nauta, Maarten; Havelaar, Arie H; Fels, Ine van der(Elsevier, 2006-01-25)
We discuss an application of probabilistic inversion techniques to a model of campylobacter transmission in chicken processing lines. Such techniques are indicated when we wish to quantify a model which is new and perhaps unfamiliar to the expert community. In this case there are no measurements for estimating model parameters, and experts are typically unable to give a considered judgment. In such cases, experts are asked to quantify their uncertainty regarding variables which can be predicted by the model. The experts’ distributions (after combination) are then pulled back onto the parameter space of the model, a process termed “probabilistic inversion”. This study illustrates two such techniques, iterative proportional fitting (IPF) and PARmeter fitting for uncertain models (PARFUM). In addition, we illustrate how expert judgement on predicted observable quantities in combination with probabilistic inversion may be used for model validation and/or model criticism.
Matthijsen, A J C M; Kooi, E S(Elsevier, 2006-06-30)
In the context of spatial planning the Dutch Ministry of Housing, Spatial Planning and the Environment asked the Centre for External Safety of the National Institute for Public Health and the Environment (RIVM) to advice on safe distances pertaining to hydrogen filling stations. The RIVM made use of failure modeling and parameters for calculating the distance in detail. An imaginary hydrogen filling station for cars is used in the determination of ‘external safety’ or third party distances for the installations and the pipe work for three different sizes of hydrogen filling stations. For several failure scenarios ‘effect’ distances are calculated for car filling at 350 and 700 bar. Safe distances of filling stations from locations where people live and work appear to be similar for compressed hydrogen, gasoline/petrol and compressed natural gas. Safe distances for LPG are greater. A filling unit for hydrogen can be placed at gasoline/petrol-filling stations without increasing safety distances
Velden, Peter G van der; Kleber, Rolf J; Christiaanse, B; Gersons, Berthold P R; Marcelissen, Frans G H; Drogendijk, Annelieke N; Grievink, Linda; Olff, Miranda; Meewisse, Mariel L(2006-08-01)
This 4-year prospective study (N=662) of victims of a fireworks disaster examines the independent predictive value of peritraumatic dissociation for self-reported intrusions, avoidance reactions, and posttraumatic stress disorder (PTSD) symptom severity at both 18-months (T2) and almost 4-years postdisaster (T3). Peritraumatic dissociation was measured 2-3 weeks after the disaster (T1). Hierarchical multiple regression analyses revealed that peritraumatic dissociation was not a strong independent predictor for intrusions and avoidance reactions and PTSD symptom severity at T2 or at T3 above initial intrusions, avoidance reactions, and psychological distress (T1). Results suggest that an early screening procedure for peritraumatic dissociation, which is aimed at identifying disaster victims who are at risk for long-term psychological disturbances can be omitted.
Aires-de-Sousa, Marta; Boye, K; Lencastre, H de; Deplano, A; Enright, M C; Etienne, J; Friedrich, A; Harmsen, D; Holmes, A; Huijsdens, Xander W; Kearns, A M; Mellmann, A; Meugnier, H; Rasheed, J K; Spalburg, Emile; Strommenger, B; Struelens, M J; Tenover, F C; Thomas, J; Vogel, U; Westh, H; Xu, J; Witte, W(2006-02-01)
Current DNA amplification-based typing methods for bacterial pathogens often lack interlaboratory reproducibility. In this international study, DNA sequence-based typing of the Staphylococcus aureus protein A gene (spa, 110 to 422 bp) showed 100% intra- and interlaboratory reproducibility without extensive harmonization of protocols for 30 blind-coded S. aureus DNA samples sent to 10 laboratories. Specialized software for automated sequence analysis ensured a common typing nomenclature.
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