Protective behaviour of citizens to transport accidents involving hazardous materials: A discrete choice experiment applied to populated areas nearby waterways

Background To improve the information for and preparation of citizens at risk to hazardous material transport accidents, a first important step is to determine how different characteristics of hazardous material transport accidents will influence citizens' protective behaviour. However, quantitative studies investigating citizens' protective behaviour in case of hazardous material transport accidents are scarce. Methods A discrete choice experiment was conducted among subjects (19-64 years) living in the direct vicinity of a large waterway. Scenarios were described by three transport accident characteristics: odour perception, smoke/vapour perception, and the proportion of people in the environment that were leaving at their own discretion. Subjects were asked to consider each scenario as realistic and to choose the alternative that was most appealing to them: staying, seekin

Insulin and IGF1 signalling pathways in human astrocytes <i>in vitro</i> and <i>in vivo</i>; characterisation, subcellular localisation and modulation of the receptors.

Background The insulin/IGF1 signalling (IIS) pathways are involved in longevity regulation and are dysregulated in neurons in Alzheimer’s disease (AD). We previously showed downregulation in IIS gene expression in astrocytes with AD-neuropathology progression, but IIS in astrocytes remains poorly understood. We therefore examined the IIS pathway in human astrocytes and developed models to reduce IIS at the level of the insulin or the IGF1 receptor (IGF1R). Results We determined IIS was present and functional in human astrocytes by immunoblotting and showed astrocytes express the insulin receptor (IR)-B isoform of Ir. Immunocytochemistry and cell fractionation followed by western blotting revealed the phosphorylation status of insulin receptor substrate (IRS1) affects its subcellular localisation. To validate IRS1 expression patterns observed in culture, expression of key pathway components was assessed on post-mortem AD and control tissue using immunohistochemistry. Insulin signalling was impaired in cultured astrocytes by treatment with insulin + fructose and resulted in decreased IR and Akt phosphorylation (pAkt S473). A monoclonal antibody against IGF1R (MAB391) induced degradation of IGF1R receptor with an associated decrease in downstream pAkt S473. Neither treatment affected cell growth or viability as measured by MTT and Cyquant® assays or GFAP immunoreactivity. Discussion IIS is functional in astrocytes. IR-B is expressed in astrocytes which differs from the pattern in neurons, and may be important in differential susceptibility of astrocytes and neurons to insulin resistance. The variable presence of IRS1 in the nucleus, dependent on phosphorylation pattern, suggests the function of signalling molecules is not confined to cytoplasmic cascades. Down-regulation of IR and IGF1R, achieved by insulin + fructose and monoclonal antibody treatments, results in decreased downstream signalling, though the lack of effect on viability suggests that astrocytes can compensate for changes in single pathways. Changes in signalling in astrocytes, as well as in neurons, may be important in ageing and neurodegeneration

The effect of perceived risks on the demand for vaccination: results from a discrete choice experiment.

The demand for vaccination against infectious diseases involves a choice between vaccinating and not vaccinating, in which there is a trade-off between the benefits and costs of each option. The aim of this paper is to investigate these trade-offs and to estimate how the perceived prevalence and severity of both the disease against which the vaccine is given and any vaccine associated adverse events (VAAE) might affect demand. A discrete choice experiment (DCE) was used to elicit stated preferences from a representative sample of 369 U.K. mothers of children below 5 years of age, for three hypothetical vaccines. Cost was included as an attribute, which enabled estimation of the willingness to pay for different vaccines having differing levels of the probability of occurrence and severity of both the infection and VAAE. The results suggest that the severity of the health effects associated with both the diseases and VAAEs exert an important influence on the demand for vaccination, whereas the probability of these events occurring was not a significant predictor. This has important implications for public health policy, which has tended to focus on the probability of these health effects as the main influence on decision making. Our results also suggest that anticipated regrets about the consequences of making the wrong decision also exert an influence on demand