Showing papers by "Defence Science and Technology Laboratory published in 2008"

A practitioner's guide to working dog welfare

Abstract: Research conducted by the Anthrozoology Institute and the Defence Science and Technology Laboratory has shown that many working dogs exhibit high levels of physiologic stress in response to kenneling (Hiby et al., 2006; Rooney et al., 2007a). Furthermore, these dogs tend to perform poorly during training, establishing links between welfare and working ability (Rooney et al., 2005, 2007b). Subsequently, we have been studying how kenneling affects welfare and working ability. Specifically, we have investigated which elements within housing and husbandry influence welfare, which of these seem to be the most important, and how environmental enrichment (e.g. feeding devices) can affect welfare and working ability. This paper draws together results from all of these studies, identifying signs that may be indicative of compromised welfare, and providing guidelines, based on scientific evidence, for how to improve kenneled working dog welfare. It reproduces an unpublished guide designed to primarily inform and advise practitioners who are responsible for caring for, and/or handling working dogs. This paper aims to ensure that practitioners are updated of the most recent advances in working dog welfare, and hence many of the studies summarized here are yet to be published in full, in peer-reviewed journals.

Explosives under pressure - the crystal structure of gamma-RDX as determined by high-pressure X-ray and neutron diffraction

Abstract: Using a combination of X-ray single crystal and neutron powder diffraction, the crystal structure of the high-pressure γ-form of RDX has been determined at 5.2 GPa and shows that the RDX molecules adopt different conformations compared to the conformation found in the ambient-pressure α-form.

Tularemia: Current Diagnosis and Treatment Options

Abstract: Tularemia is an infection caused by Francisella tularensis with a worldwide distribution and diverse clinical manifestations. Limitations in both culture and serologic testing have led to substantial research into new diagnostic techniques and their clinical application, with PCR testing as the best example. This review focuses on the utility of culture, PCR and serologic testing for tularemia. In addition, we also review the evidence to support different therapeutic options for tularemia, highlighting both the most effective supporting evidence for therapeutic recommendations as well as gaps in current knowledge. We conclude the article with suggestions regarding potential areas for future research.

An Ontology-Centric Approach to Sensor-Mission Assignment

Abstract: Sensor-mission assignment involves the allocation of sensor and other information-providing resources to missions in order to cover the information needs of the individual tasks in each mission. This is an important problem in the intelligence, surveillance, and reconnaissance (ISR) domain, where sensors are typically over-subscribed, and task requirements change dynamically. This paper approaches the sensor-mission assignment problem from a Semantic Web perspective: the core of the approach is a set of ontologies describing mission tasks, sensors, and deployment platforms. Semantic reasoning is used to recommend collections of types of sensors and platforms that are known to be "fit-for-purpose" for a particular task, during the mission planning process. These recommended solutions are used to constrain a search for available instances of sensors and platforms that can be allocated at mission execution-time to the relevant tasks. An interface to the physical sensor environment allows the instances to be configured to operate as a coherent whole and deliver the necessary data to users. Feedback loops exist throughout, allowing re-planning of the sensor-task fitness, reallocation of instances, and reconfiguration of the sensor network.

Recombinant Bacillus subtilis Expressing the Clostridium perfringens Alpha Toxoid Is a Candidate Orally Delivered Vaccine against Necrotic Enteritis

Abstract: Recombinant Bacillus subtilis endospores have been used to vaccinate against tetanus and anthrax. In this work, we have developed spores that could be used to vaccinate against Clostridium perfringens alpha toxin and that could be used to protect against gas gangrene in humans and necrotic enteritis in poultry. The primary active agent in both cases is alpha toxin. A carboxy-terminal segment of the alpha toxin gene (cpa) fused to the glutathione-S-transferase (GST) gene was cloned in B. subtilis such that the encoded GST-Cpa247-370 polypeptide had been expressed in the following three different ways: expression in the vegetative cell, expression on the surface of the spore coat (fused to the CotB spore coat protein), and a combined approach of spore coat expression coupled with expression in the vegetative cell. Mice immunized orally or nasally with three doses of recombinant spores that carried GST-Cpa247-370 on the spore surface showed the most striking responses. This included seroconversion with anti-Cpa247-370-specific immunoglobulin G (IgG) responses in their sera, a Th2 bias, and secretory IgA responses in saliva, feces, and lung samples. Neutralizing IgG antibodies to alpha toxin were detected using in vitro and in vivo assays, and a toxin challenge established protection. Mice immunized nasally or orally with recombinant spores were protected against a challenge with 12 median lethal doses of alpha toxin. Existing use of spores as competitive exclusion agents in animal feeds supports their use as a potentially economical and heat-stable vaccine for the poultry industry.

Structure of the exosporium and sublayers of spores of the Bacillus cereus family revealed by electron crystallography

Abstract: We report on the first step in mapping out the spatial location of structural proteins within the exosporium, namely a description of its three-dimensional architecture. Using electron microscopy and image analysis, we have characterized crystalline fragments from the exosporium of Bacillus cereus, B. thuringiensis and B. anthracis strains and identified up to three distinct crystal types. Type I and type II crystals were examined in three dimensions and shown to form arrays of interlinked crown-like structures each enclosing a cavity approximately 26-34 A deep with threefold symmetry. The arrays appear to be permeated by tunnels allowing access from one surface to the other, possibly indicating that the exosporium forms a semi-permeable barrier. The pore size of approximately 23-34 A would allow passage of the endospore germinants, alanine or inosine but not degradative enzymes or antibodies. Thus the structures appear compatible with a protective role for the exosporium. Furthermore the outermost crystalline layer must act as a scaffold for binding the BclA protein that contributes to the 'hairy nap' layer. The array of crowns may also act as a matrix for the binding or adsorption of other proteins that have been identified in the exosporium such as GroEL, immune inhibitor A and arginase.

Characterization and deposition of respirable large- and small-particle bioaerosols.

Abstract: The deposition patterns of large-particle microbiological aerosols within the respiratory tract are not well characterized. A novel system (the flow-focusing aerosol generator [FFAG]) which enables the generation of large (>10-microm) aerosol particles containing microorganisms under laboratory conditions was characterized to permit determination of deposition profiles within the murine respiratory tract. Unlike other systems for generating large aerosol particles, the FFAG is compatible with microbiological containment and the inhalational challenge of animals. By use of entrapped Escherichia coli cells, Bacillus atrophaeus spores, or FluoSphere beads, the properties of aerosols generated by the FFAG were compared with the properties of aerosols generated using the commonly available Collison nebulizer, which preferentially generates small (1- to 3-microm) aerosol particles. More entrapped particulates (15.9- to 19.2-fold) were incorporated into 9- to 17-microm particles generated by the FFAG than by the Collison nebulizer. The 1- to 3-microm particles generated by the Collison nebulizer were more likely to contain a particulate than those generated by the FFAG. E. coli cells aerosolized using the FFAG survived better than those aerosolized using the Collison nebulizer. Aerosols generated by the Collison nebulizer and the FFAG preferentially deposited in the lungs and nasal passages of the murine respiratory tract, respectively. However, significant deposition of material also occurred in the gastrointestinal tract after inhalation of both the small (89.7%)- and large (61.5%)-particle aerosols. The aerosols generated by the Collison nebulizer and the FFAG differ with respect to mass distribution, distribution of the entrapped particulates, bacterial survival, and deposition within the murine respiratory tract.

Foreign Fighters and the Case of Chechnya: A Critical Assessment

Abstract: The aim of this article is to explore and analyze the role of foreign fighters in the recent episodes of Russo–Chechen violence in the North Caucasus. The article begins by offering a preliminary theoretical consideration of foreign fighters, indicating how the events in Afghanistan combined with the development of a Salafi-Jihadist movement that would shape subsequent conflicts in the North Caucasus throughout the 1990s. The article will then move on to identify the role of Arab foreign fighters in Chechnya, demonstrating how a complex local and global social networks enable and motivate volunteers.

Burkholderia pseudomallei: animal models of infection.

Abstract: A range of animal models of Burkholderia pseudomallei infection have been reported, and the host species differ widely both in their susceptibility to infection and in the pathogenesis of disease. In mice, and depending on the route of infection, dose, and mouse strain, the disease can range from a chronic, and in some cases, an apparently latent infection to an acute fulminant disease. Alternative small animal models of infection include diabetic rats or hamsters. Larger animal models of disease have not yet been fully developed. It is not clear which of the small animal models of melioidosis most accurately reflect disease in humans. However, the findings that diabetic rats are susceptible to infection, that some strains of mice can develop persistent subclinical infections that can spontaneously reactivate, and that inhalation exposure generally results in more acute disease suggest that these different models mimic different aspects of human melioidosis.

An overview of biological markers of exposure to chemical warfare agents.

Abstract: An overview is given of biological markers of exposure to chemical warfare agents. Metabolites, protein, and/or DNA adducts have been identified for most nerve agents and vesicants and validated in experimental animals or in a small number of human exposures. For several agents, metabolites derived from hydrolysis are unsatisfactory biomarkers of exposure because of background levels in the human population. These are assumed to result from environmental exposure to commercial products that contain these hydrolysis products or chemicals that are metabolized to them. In these cases, metabolites derived from glutathione pathways, or covalent adducts with proteins or DNA, provide more definitive biomarkers. Biomarkers for cyanide and phosgene are unsatisfactory as indicators of chemical warfare exposure because of other sources of these chemicals or their metabolites.

Inhibitory potency against human acetylcholinesterase and enzymatic hydrolysis of fluorogenic nerve agent mimics by human paraoxonase 1 and squid diisopropyl fluorophosphatase.

Abstract: A wide range of toxic organophosphorus pesticides and nerve agents is effectively hydrolyzed by the structurally related phosphotriesterase enzymes paraoxonase (PON1) from human plasma and diisopropyl fluorophosphatase (DFPase) from the squid Loligo vulgaris. Both enzymes have potential use as medical countermeasures and decontaminants. Enhanced enzymatic activity, stereochemical preference, and substrate variety are still the focus of ongoing research. Derivatives of pesticides and nerve agents bearing a fluorogenic leaving group were introduced for high-throughput screening of mutant libraries recently. We report the inhibitory potency of fluorogenic organophosphorus compounds with three different leaving groups [3-chloro-7-oxy-4-methylcoumarin, 7-oxy-4-methylcoumarin, 7-oxy-4-(trifluoromethyl)coumarin] toward human acetylcholinesterase (AChE) and report kinetic data for the enzymatic hydrolysis of these compounds by PON1 and DFPase. This is the first report of the hydrolysis of a substrate bearing a P-O bond to the leaving group by DFPase (its activity was believed to be restricted to cleavage of P-F and P-CN bonds). The reactivity of the enzymes toward the substrates is explained on the basis of structural reasoning and computational docking studies. We demonstrate that fluorogenic organophosphorus compounds can serve as valuable models for enzyme screening but also show that differences and limitations exist and have to be taken into account. The importance of using protein from human sources to obtain toxicological data for potential in vivo use is highlighted.

Experimental respiratory anthrax infection in the common marmoset (Callithrix jacchus).

Abstract: Inhalational anthrax is a rare but potentially fatal infection in man. The common marmoset (Callithrix jacchus) was evaluated as a small non-human primate (NHP) model of inhalational anthrax infection, as an alternative to larger NHP species. The marmoset was found to be susceptible to inhalational exposure to Bacillus anthracis Ames strain. The pathophysiology of infection following inhalational exposure was similar to that previously reported in the rhesus and cynomolgus macaque and humans. The calculated LD(50) for B. anthracis Ames strain in the marmoset was 1.47 x 10(3) colony-forming units, compared with a published LD(50) of 5.5 x 10(4) spores in the rhesus macaque and 4.13 x 10(3) spores in the cynomolgus macaque. This suggests that the common marmoset is an appropriate alternative NHP and will be used for the evaluation of medical countermeasures against respiratory anthrax infection.

Body wearable antennas for UHF/VHF

Abstract: The development of antennas which can be worn on the body is of increasing interest within both the military and civil domain. Body wearable antennas present a considerable design challenge, particularly as most applications require the antenna to be unobtrusive and low-profile. The majority of recent work has concentrated on antennas for WLAN or UWB frequencies. At these frequencies the antennas are relatively small and can be made low-profile to fit on the body. It is also possible to incorporate a ground-plane (such as a PIFA or patch antenna) which significantly reduces the effect of the body on antenna performance. In this paper, antennas which operate across the 100-500 MHz band are considered. At these lower frequencies the antennas are physically larger and cannot incorporate an effective ground-plane so the effect of the body is significant. In this work it was assumed simultaneous coverage of the entire band and omnidirectional radiation patterns were required. This paper discusses the antennas considered, and those selected to meet these challenging requirements. Design of the antennas using computational electromagnetics software is presented. The development of prototype antennas is also presented, along with results of antenna pattern measurements.

The effect of feeding enrichment upon reported working ability and behavior of kenneled working dogs.

Abstract: It is widely recommended that kenneled dogs are provided with environmental enrichment such as toys or feeding devices. However, the adoption of enrichment for military working dogs is impeded by a widespread belief that it reduces their motivation to work. Handlers of 22 working German Shepherd dogs were asked to rate their dogs on 11 attributes pertaining to working ability, related behavioral traits, and health. Eight of the dogs were then provided with daily feeding enrichment for 4 months, while the remainder were given equivalent human attention. The same 11 traits were scored again following the enrichment period: 10 changed little over the period while handlers' reports of their dogs' Ability to learn from being rewarded increased significantly. Changes for all attributes were virtually identical in enriched and control dogs. We conclude that if correctly managed, feeding enrichment can be introduced to kenneled working dogs without any reported detrimental effects upon working ability, health, or behavior.

International Military Leaders' Survey on Operational Stress

Abstract: Despite the importance of military leaders in moderating the impact of deployment stressors on unit members, little attention has focused on the training leaders receive in managing unit stress. As part of a NATO Research Panel (Human Factors and Medicine (HFM)-081/Research and Technology Organization Task Group (RTG)), 16 nations participated in a needs assessment survey of military leaders who had returned from an operation within the previous 2 years. Findings from 172 leaders emphasized the lack of training specifically geared for leaders to address operational stress issues for unit members and their families and the need for integrated mental health support across the deployment cycle. In general, most leaders regarded stress-related mental health problems as normal and were supportive of help-seeking. The information obtained here was used to develop a Human Factors and Medicine -081/RTG Leader's Guide on operational stress.

Proposal of a framework for evaluating military surveillance systems for early detection of outbreaks on duty areas

Abstract: In recent years a wide variety of epidemiological surveillance systems have been developed to provide early identification of outbreaks of infectious disease. Each system has had its own strengths and weaknesses. In 2002 a Working Group of the Centers for Disease Control and Prevention (CDC) produced a framework for evaluation, which proved suitable for many public health surveillance systems. However this did not easily adapt to the military setting, where by necessity a variety of different parameters are assessed, different constraints placed on the systems, and different objectives required. This paper describes a proposed framework for evaluation of military syndromic surveillance systems designed to detect outbreaks of disease on operational deployments. The new framework described in this paper was developed from the cumulative experience of British and French military syndromic surveillance systems. The methods included a general assessment framework (CDC), followed by more specific methods of conducting evaluation. These included Knowledge/Attitude/Practice surveys (KAP surveys), technical audits, ergonomic studies, simulations and multi-national exercises. A variety of military constraints required integration into the evaluation. Examples of these include the variability of geographical conditions in the field, deployment to areas without prior knowledge of naturally-occurring disease patterns, the differences in field sanitation between locations and over the length of deployment, the mobility of military forces, turnover of personnel, continuity of surveillance across different locations, integration with surveillance systems from other nations working alongside each other, compatibility with non-medical information systems, and security. A framework for evaluation has been developed that can be used for military surveillance systems in a staged manner consisting of initial, intermediate and final evaluations. For each stage of the process parameters for assessment have been defined and methods identified. The combined experiences of French and British syndromic surveillance systems developed for use in deployed military forces has allowed the development of a specific evaluation framework. The tool is suitable for use by all nations who wish to evaluate syndromic surveillance in their own military forces. It could also be useful for civilian mobile systems or for national security surveillance systems.

Study of the Effect of Additive Particle Size on Non‐ideal Explosive Performance

Abstract: Detonation performance of non-ideal RDX-based compositions was studied. Charges of phlegmatised RDX containing 30% of two types of aluminium powders, coarse aluminium oxide or fine lithium fluoride particles were tested. The research concerning influence of inert and reactive additives on the detonation velocity and quasi-static pressure was carried out. To estimate the degree of afterburning of the detonation products and reactive particles, closed explosions were performed in a chamber filled with different atmospheres. Explosion residues were also analysed. Gasdynamical and thermochemical calculations were also performed for the tested explosive compositions.

Terrestrial laser scanning for assessing the risk of slope instability along transport corridors

Abstract: Transport networks play a crucial part in the global economy, with roads and railways being of particular importance at regional and national scales. However, roads and railways are founded on earthworks such as embankments, which can be susceptible to slope failure. Slope instability is a costly problem, which can lead to travel disruption, and injury or loss of life. Earthwork stability assessment is therefore a critical activity for management bodies. However, current approaches are largely limited to hazardous onfoot site inspections. Although high resolution geospatial datasets are becoming increasingly available, there is currently a mismatch between the availability of these datasets, and the ability to use this data in support of decision making. This paper presents one aspect of an integrated methodology for risk assessment in transport corridor environments. The potential of terrestrial laser scanning (TLS) for assessment of slope deformation and failure is examined through application to two test sites in the north of England. The first site is a full-scale test embankment, while the second is a modern highway embankment. Results have shown that for both sites, multi-temporal TLS surveys facilitate the detection of minor changes, such as soil creep and surface runoff. However, vegetation was found to be a complicating factor, contributing to registration errors between individual scans. This was resolved through the use of a least squares surface matching algorithm, which ultimately facilitated detection of change at the centimetric level. These results confirm the potential of TLS for embankment stability assessment, while highlighting some of the practical limitations. * Corresponding author.

Sero-characterization of lipopolysaccharide from Burkholderia thailandensis.

Abstract: We report the successful purification of lipopolysaccharide (LPS) from Burkholderia thailandensis, a Gram-negative bacterium, closely related to the highly pathogenic organisms B. pseudomallei and B. mallei. Burkholderia thailandensis LPS is shown to cross-react with rabbit and mouse sera obtained from inoculation with B. pseudomallei or B. mallei, respectively. These data suggest that B. thailandensis LPS shares similar structural features with LPS molecules from highly pathogenic Burkholderia species. This information may prove useful in ongoing efforts to develop novel vaccines and/or diagnostic reagents.

Development of aptamers specific for potential diagnostic targets in Burkholderia pseudomallei.

Abstract: Improved diagnostic reagents would be of considerable benefit in enhancing the specificity and sensitivity of rapid assays for Burkholderia pseudomallei, the causative agent of melioidosis. The purpose of this work is to develop aptamers, high affinity RNA-based molecular recognition molecules, which could be used as reagents for identification of the whole organism in assays of biological samples. Data are presented demonstrating the purification of recombinant B. pseudomallei secreted or surface-exposed macromolecules, which have been expressed in Escherichia coli, and the initial stages of aptamer generation using these recombinant proteins. Future studies will focus upon the expansion of this methodology to include other target macromolecules located on or near the outer membrane of this organism.

The use of dopants in high field asymmetric waveform spectrometry

Abstract: Ion mobility spectrometry (IMS) is proven core technology for the gas-phase detection of chemical warfare (CW) agents. One disadvantage of IMS technology is that ions of similar mobility cannot readily be resolved, resulting in false alarm responses and a loss of user confidence. High field asymmetric waveform spectrometry (HiFAWS) is an emerging technology for the gas-phase detection of CW agents. Of particular interest is the potential of a HiFAWS-based platform to reduce the number of false alarms by resolving ions that cannot be discriminated using IMS. It has been demonstrated that a water clustering/declustering mechanism can be a dominant process in HiFAWS. Ions that cannot be discriminated in IMS because they possess the same low field mobility value can be resolved using HiFAWS due to differences in the extent of low field ion solvation and high field ion desolvation. When operating in complex environments such as those potentially experienced in military and security arenas, IMS systems commonly employ internal dopants to reduce the number of background responses. It is possible that HiFAWS systems may also require the use of internal dopants for the same reason. It has been demonstrated that dopants employed for use in IMS may not be suitable for use in HiFAWS.

The use of doxycycline as a protectant against sulphur mustard in HaCaT cells.

Abstract: As part of an ongoing programme on medical countermeasures against the chemical warfare agent sulphur mustard (HD) and set against the background of the involvement of matrix metalloproteinases (MMPs) in the pathology of HD-induced vesication processes, the potentially beneficial effects of doxycycline on cell attachment was determined in confluent HaCaT cell cultures exposed to HD. Doxycycline was found to inhibit to a significant extent the tendency of HD-exposed cells to detach from the growth substrate, however, analysis of the metabolic activity of the adherent cells indicated that doxycycline treatment did not maintain cell viability. It was confirmed that apoptosis was the predominant mode of HD-induced cell death. The results suggested that doxycycline and other MMP inhibitors may have a role to play in therapeutic intervention against HD exposure, but only as part of a combination therapy. The specific value of protease inhibitors in this capacity remains to be determined.

CpG used as an adjuvant for an adenovirus-based Venezuelan equine encephalitis virus vaccine increases the immune response to the vector, but not to the transgene product.

Abstract: An adenovirus-based (ad-based) vaccine delivering antigens from the Alphavirus Venezuelan equine encephalitis virus (VEEV) is a strategy that offers clinical potential. A vaccine against VEEV is desirable because of the re-emerging nature of this virus, and also the potential that it may be used as a biological weapon. This study was designed to investigate whether the co-administration of CpG oligodeoxynucleotides (ODNs) with an ad-based VEEV vaccine could enhance the protective efficacy of the vaccine. We report that the co-administration of CpG ODN was unable to increase VEEV-specific antibody responses in mice, and was unable to increase the protective efficacy of the vaccine against aerosol challenge with virulent VEEV. However, it was noted that antibody responses directed against the adenovirus vaccine vector were increased, which may be detrimental, particularly in the context of homologous boosting.

Changing behaviours in defence acquisition: a game theory approach

Abstract: Why do so many major defence contracts fail to deliver to the contractually agreed performance, time and cost requirements? This paper identifies the conspiracy of optimism as an important factor in the initiation of many projects. Using a combination of Game Theory and participatory workshops, we formulate a theory on the conspiracy of optimism and test it experimentally. This work forms part of a culture and behaviour change initiative within Defence Acquisition involving the Ministry of Defence and many defence contractors.

Development of a model of hookworm infection exhibiting salient characteristics of human infection.

Abstract: Patent and pathologic infections of the human hookworm Necator americanus were established in the common marmoset (Callithrix jacchus). In a pilot study, a laboratory strain of N. americanus was compared with a fresh field isolate. Pathology was more severe in animals infected with a fresh isolate. In all animals, infection was associated with increased total plasma IgE and production of IgG specific to adult worm excretory/secretory (ES) products. Histamine was released by basophils in response to IgE, ES products, and a recombinant hookworm allergen, calreticulin. The pilot study indicated the potential of this animal model of hookworm infection and led us to investigate the consequences of infecting a further cohort with the fresh field isolate. This second study confirmed our initial findings, that it is possible to investigate the human hookworm N. americanus in a model exhibiting many of the characteristics of the immunology of hookworm infection in its definitive host.