| 1. |
- Morris, A, et al.
(författare)
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The Development of a Multidisciplinary System to Understand Causal Factors in Road Crashes
- 2006
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Ingår i: 42nd Annual Human Factors and Ergonomics Society of Australia Conference 2006, HFESA 2006. - 9781622769599 ; , s. 31-38
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The persistent lack of crash causation data to help inform and monitor road and vehicle safety policy is a major obstacle. Data are needed to assess the performance of road and vehicle safety stakeholders and is needed to support the development of further actions. A recent analysis conducted by the European Transport Safety Council identified that there was no single system in place that could meet all of the needs and that there were major gaps including in-depth crash causation information. This paper describes the process of developing a data collection and analysis system designed to fill these gaps. A project team with members from 7 countries was set up to devise appropriate variable lists to collect crash causation information under the following topic levels: accident, road environment, vehicle, and road user, using two quite different sets of resources: retrospective detailed police reports (n=1300) and prospective, independent, on-scene accident research investigations (n=1000). Data categorisation and human factors analysis methods based on Cognitive Reliability and Error Analysis Method (Hollnagel, 1998) were developed to enable the causal factors to be recorded, linked and understood. A harmonised, prospective "on-scene" method for recording the root causes and critical events of road crashes was developed. Where appropriate, this includes interviewing road users in collaboration with more routine accident investigation techniques. The typical level of detail recorded is a minimum of 150 variables for each accident. The project will enable multidisciplinary information on the circumstances of crashes to be interpreted to provide information on the causal factors. This has major applications in the areas of active safety systems, infrastructure and road safety, as well as for tailoring behavioural interventions. There is no direct model available internationally that uses such a systems based approach.
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| 2. |
- Patel, Jayendra Z., et al.
(författare)
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Chiral 1,3,4-Oxadiazol-2-ones as Highly Selective FAAH Inhibitors
- 2013
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:21, s. 8484-8496
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, identification of chiral 1,3,4-oxadiazol-2-ones as potent and selective FAAH inhibitors has been described. The separated enantiomers showed clear differences in the potency and selectivity toward both FAAH and MAGL. Additionally, the importance of the chirality on the inhibitory activity and selectivity was proven by the simplification approach by removing a methyl group at the 3-position of the 1,3,4-oxadiazol-2-one ring. The most potent compound of the series, the S-enantiomer of 3-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-327A, Si), inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 mu M), whereas its corresponding R-enantiomer 52 showed only moderate inhibition toward hrFAAH (IC50 = 0.24 mu M). In contrast to hrFAAH, R-enantiomer 52 was more potent in inhibiting the activity of hrMAGL compared to S-enantiomer 51 (IC50 = 4.0 mu M and 16% inhibition at 10 mu M, respectively). The FAAH selectivity of the compound Si over the supposed main off-targets, MAGL and COX, was found to be >900-fold. In addition, activity-based protein profiling (ABPP) indicated high selectivity over other serine hydrolases. Finally, the selected Senantiomers 51, 53, and 55 were shown to be tight binding, slowly reversible inhibitors of the hrFAAH.
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