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Black R.M.,UK Defence Science and Technology Laboratory
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2010

This paper provides a short historical overview of the development of bioanalytical methods for chemical warfare (CW) agents and their biological markers of exposure, with a more detailed overview of methods for organophosphorus nerve agents. Bioanalytical methods for unchanged CW agents are used primarily for toxicokinetic/toxicodynamic studies. An important aspect of nerve agent toxicokinetics is the different biological activity and detoxification pathways for enantiomers. CW agents have a relatively short lifetime in the human body, and are hydrolysed, metabolised, or adducted to nucleophilic sites on macromolecules such as proteins and DNA. These provide biological markers of exposure. In the past two decades, metabolites, protein adducts of nerve agents, vesicants and phosgene, and DNA adducts of sulfur and nitrogen mustards, have been identified and characterized. Sensitive analytical methods have been developed for their detection, based mainly on mass spectrometry combined with gas or liquid chromatography. Biological markers for sarin, VX and sulfur mustard have been validated in cases of accidental and deliberate human exposures. The concern for terrorist use of CW agents has stimulated the development of higher throughput analytical methods in support of homeland security. © 2010. Source

Pope D.J.,UK Defence Science and Technology Laboratory
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

In the aftermath of the London '7/7' attacks in 2005, UK government agencies required the development of a quick-running tool to predict the weapon and injury effects caused by the initiation of a person borne improvised explosive device (PBIED) within crowded metropolitan environments. This prediction tool, termed the HIP (human injury predictor) code, was intended to: - assist the security services to encourage favourable crowd distributions and densities within scenarios of 'sensitivity'; - provide guidance to security engineers concerning the most effective location for protection systems; - inform rescue services as to where, in the case of such an event, individuals with particular injuries will be located; - assist in training medical personnel concerning the scope and types of injuries that would be sustained as a consequence of a particular attack; - assist response planners in determining the types ofmedical specialists (burns, traumatic amputations, lungs, etc.) required and thus identify the appropriate hospitals to receive the various casualty types. This document describes the algorithms used in the development of this tool, together with the pertinent underpinning physical processes. From its rudimentary beginnings as a simple spreadsheet, theHIP code now has a graphical user interface (GUI) that allows three-dimensional visualization of results and intuitive scenario set-up. The code is underpinned by algorithms that predict the pressure and momentum outputs produced by PBIEDs within open and confined environments, aswell as the trajectories of shrapnel deliberately placed within the device to increase injurious effects. Further logic has been implemented to transpose these weapon effects into forms of human injury depending on where individuals are located relative to the PBIED. Each crowd member is subdivided into representative body parts, each of which is assigned an abbreviated injury score after a particular calculation cycle. The injury levels of each affected body part are then summated and a triage state assigned for each individual crowd member based on the criteria specified within the 'injury scoring system'. To attain a comprehensive picture of a particular event, it is important that a number of simulations, using what is substantively the same scenario, are undertaken with natural variation being applied to the crowd distributions and the PBIED output. Accurate mathematical representation of such complex phenomena is challenging, particularly as the code must be quick-running to be of use to the stakeholder community. In addition to discussing the background and motivation for the algorithm and GUI development, this document also discusses the steps taken to validate the tool and the plans for further functionality implementation. © 2011 The Royal Society. Source

Griffiths G.D.,UK Defence Science and Technology Laboratory
Toxins | Year: 2011

The toxin ricin has long been understood to have potential for criminal activity and there has been concern that it might be used as a mass-scale weapon on a military basis for at least two decades. Currently, the focus has extended to encompass terrorist activities using ricin to disrupt every day activities on a smaller scale. Whichever scenario is considered, there are features in common which need to be understood; these include the knowledge of the toxicity from ricin poisoning by the likely routes, methods for the detection of ricin in relevant materials and approaches to making an early diagnosis of ricin poisoning, in order to take therapeutic steps to mitigate the toxicity. This article will review the current situation regarding each of these stages in our collective understanding of ricin and how to defend against its use by an aggressor.© 2011 by the authors; licensee MDPI, Basel, Switzerland. Source

Thomas R.J.,UK Defence Science and Technology Laboratory
Virulence | Year: 2013

Particle size dictates where aerosolized pathogens deposit in the respiratory tract, thereafter the pathogens potential to cause disease is influenced by tissue tropism, clearance kinetics and the host immunological response. This interplay brings pathogens into contact with a range of tissues spanning the respiratory tract and associated anatomical structures. In animal models, differential deposition within the respiratory tract influences infection kinetics for numerous select agents. Greater numbers of pathogens are required to infect the upper (URT) compared with the lower respiratory tract (LRT), and in comparison the URT infections are protracted with reduced mortality. Pathogenesis in the URT is characterized by infection of the URT lymphoid tissues, cervical lymphadenopathy and septicemia, closely resembling reported human infections of the URT. The olfactory, gastrointestinal, and ophthalmic systems are also infected in a pathogen-dependent manner. The relevant literature is reviewed with respect to particle size and infection of the URT in animal models and humans. © 2013 Landes Bioscience. Source

Riches J.R.,UK Defence Science and Technology Laboratory
Journal of analytical toxicology | Year: 2012

On October 26, 2002, Russian Special Forces deployed a chemical aerosol against Chechen terrorists to rescue hostages in the Dubrovka theatre. Its use confirmed Russian military interest in chemicals with effects on personnel and caused 125 deaths through a combination of the aerosol and inadequate medical care. This study provides evidence from liquid chromatography-tandem mass spectrometry analysis of extracts of clothing from two British survivors, and urine from a third survivor, that the aerosol comprised a mixture of two anaesthetics--carfentanil and remifentanil--whose relative proportions this study was unable to identify. Carfentanil and remifentanil were found on a shirt sample and a metabolite called norcarfentanil was found in a urine sample. This metabolite probably originated from carfentanil. Source

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