Showing papers by "Defence Science and Technology Laboratory published in 2007"
TL;DR: It is concluded that urinary C/C is a valuable indicator of acute stress and hence welfare status in dogs, but that behavioural measures need to be interpreted with caution due to individuality in coping strategies.
214 citations
TL;DR: Damage Control Resuscitation is a novel concept that draws together a series of technical and organisational advances in combat casualty care and encapsulates the established concept of damage control surgery (DCS).
Abstract: Damage Control Resuscitation (DCR) is a novel concept that draws together a series of technical and organisational advances in combat casualty care. It is consistent with and encapsulates the established concept of damage control surgery (DCS).
150 citations
TL;DR: The tyrosine adducts with soman and tabun were detected in guinea pigs receiving therapy 7 days following subcutaneous administration of five times the LD50 dose of the respective nerve agent.
Abstract: The organophosphorus nerve agents sarin, soman, cyclosarin and tabun phosphylate a tyrosine residue on albumin in human blood. These adducts may offer relatively long-lived biological markers of nerve agent exposure that do not ‘age’ rapidly, and which are not degraded by therapy with oximes. Sensitive methods for the detection of these adducts have been developed using liquid chromatography-tandem mass spectrometry. Adducts of all four nerve agents were detected in the blood of exposed guinea pigs being used in studies to improve medical countermeasures. The tyrosine adducts with soman and tabun were detected in guinea pigs receiving therapy 7 days following subcutaneous administration of five times the LD50 dose of the respective nerve agent. VX also forms a tyrosine adduct in human blood in vitro but only at high concentrations.
141 citations
TL;DR: Insight into the protective immune response is given and potentially important implications for the rational design of non‐living vaccines for tularemia and other intracellular pathogens are given.
Abstract: Stimulation of protective immune responses against intracellular pathogens is difficult to achieve using non-replicating vaccines. BALB/c mice immunized by intramuscular injection with killed Francisella tularensis (live vaccine strain) adjuvanted with preformed immune stimulating complexes admixed with CpG, were protected when systemically challenged with a highly virulent strain of F. tularensis (Schu S4). Serum from immunized mice was used to probe a whole proteome microarray in order to identify immunodominant antigens. Eleven out of the top 12 immunodominant antigens have been previously described as immunoreactive in F. tularensis. However, 31 previously unreported immunoreactive antigens were revealed using this approach. Twenty four (50%) of the ORFs on the immunodominant hit list belonged to the category of surface or membrane associated proteins compared to only 22% of the entire proteome. There were eight hypothetical protein hits and eight hits from proteins associated with different aspects of metabolism. The chip also allowed us to readily determine the IgG subclass bias, towards individual or multiple antigens, in protected and unprotected animals. These data give insight into the protective immune response and have potentially important implications for the rational design of non-living vaccines for tularemia and other intracellular pathogens.
115 citations
TL;DR: White matter and spinal chord showed significant variation as function of animal age, no age-related variations were recorded for grey matter and the total combined measurement uncertainty was calculated at each frequency point and is reported over representative frequency regions.
Abstract: The dielectric properties of pig cerebrospinal tissues were measured in vivo and in vitro, in the frequency range of 50 MHz–20 GHz. The total combined measurement uncertainty was calculated at each frequency point and is reported over representative frequency regions. Comparisons were made for each tissue between the two sets of data and with the literature of the past decade. The in vitro study was extended to include tissue from pigs weighing approximately 10, 50 and 250 kg to re-visit the question of the variation of dielectric properties with age. White matter and spinal chord showed significant variation as function of animal age, no age-related variations were recorded for grey matter.
108 citations
TL;DR: The sequence of the gene cluster encoding the O antigen in Francisella novicida is determined and compared to the previously reported O-antigen cluster in Francislla tularensis subsp.
Abstract: We have determined the sequence of the gene cluster encoding the O antigen in Francisella novicida and compared it to the previously reported O-antigen cluster in Francisella tularensis subsp. tularensis. Immunization with purified lipopolysaccharide (LPS) from F. tularensis subsp. tularensis or F. novicida protected against challenge with Francisella tularensis subsp. holarctica and F. novicida, respectively. The LPS from F. tularensis subsp. tularensis did not confer protection against challenge with F. novicida, and the LPS from F. novicida did not confer protection against challenge with F. tularensis subsp. holarctica. Allelic replacement mutants of F. tularensis subsp. tularensis or F. novicida which failed to produce O antigen were attenuated, but exposure to these mutants did not induce a protective immune response. The O antigen of F. tularensis subsp. tularensis appeared to be important for intracellular survival whereas the O antigen of F. novicida appeared to be critical for serum resistance and less important for intracellular survival.
103 citations
TL;DR: The refined signature-tagged mutagenesis approach developed in this study was used to efficiently identify attenuating mutants from this highly pathogenic species and could be applied to other organisms.
Abstract: Burkholderia pseudomallei, the causative agent of melioidosis, is an important human pathogen in Southeast Asia and northern Australia for which a vaccine is unavailable. A panel of 892 double signature-tagged mutants was screened for virulence using an intranasal BALB/c mouse model of infection. A novel DNA tag microarray identified 33 mutants as being attenuated in spleens, while 6 were attenuated in both lungs and spleens. The transposon insertion sites in spleen-attenuated mutants revealed genes involved in several stages of capsular polysaccharide biosynthesis and DNA replication and repair, a putative oxidoreductase, ABC transporters, and a lipoprotein that may be important in intercellular spreading. The six mutants identified as missing in both lungs and spleens were found to have insertions in recA involved in the SOS response and DNA repair; putative auxotrophs of leucine, threonine, p-aminobenzoic acid, and a mutant with an insertion in aroB causing auxotrophy for aromatic compounds were also found. Murine challenge studies revealed partial protection in BALB/c mice vaccinated with the aroB mutant. The refined signature-tagged mutagenesis approach developed in this study was used to efficiently identify attenuating mutants from this highly pathogenic species and could be applied to other organisms.
102 citations
TL;DR: The current status of vaccine development efforts against tularemia is reviewed, with more modern molecular approaches to vaccine development against this highly virulent pathogen highlighted.
Abstract: Francisella tularensis is one of the most pathogenic pathogens known, especially when disseminated as a small particle aerosol. Because of this, it was developed into a biological warfare agent by several states during the 20th century. Nowadays, concerns remain about the potential of this pathogen to cause widespread disease, tularemia, in the hands of terrorists. This has resurrected interest in methods to combat it. This article reviews the current status of vaccine development efforts against tularemia. To date most of our understanding of tularemia vaccine efficacy has been derived from the clinical and experimental use of a pragmatically attenuated live vaccine strain of F. tularensis subspecies holarctica. However, this vaccine which has been in existence for more than 50 years is still beset by regulatory issues that continue to hamper its licensure. These issues and possible solutions are highlighted, along with more modern molecular approaches to vaccine development against this highly virulent pathogen.
102 citations
TL;DR: In this paper, thin films of the nematic liquid crystal E7 supported on chemically functionalized surfaces were used to indicate the presence of vapors of the organophosphorous nerve agents sarin (GB), soman (GD), tabun (GA) and VX.
Abstract: We report use of thin films of the nematic liquid crystal E7 supported on chemically functionalized surfaces to indicate the presence of vapors of the organophosphorous nerve agents sarin (GB), soman (GD), tabun (GA) and VX. The surfaces were prepared by the deposition of metal perchlorate salts onto carboxylic acid-terminated self-assembled monolayers. When using surfaces prepared from aluminum perchlorate salts, the nematic film of E7 underwent a transition from a perpendicular orientation to a tilted or planar orientation upon exposure to vapors of GB, GD, GA or VX generated from a small drop of agent placed on a piece of filter paper. The orientational transition of the liquid crystal was readily apparent as an optical signal that was visible to the naked eye. The agent VX, which has the lowest vapor pressure of these organophosphorous nerve agents (∼140 ppb), was reported by the liquid crystal within 60 s. The agents GB, GD, and GA, which have higher vapor pressures, triggered responses in the liquid crystal that were evident within 15 s, 15 s, and 60 s, respectively. By preparing surfaces from perchlorate salts of aluminum(III), zinc(II) and iron(III) it was possible to distinguish between GB, VX and either GD or GA, thus demonstrating the feasibility of designing surfaces patterned with metal salts to detect and positively identify chemical warfare agents.
74 citations
TL;DR: The rF1+rV candidate sub-unit vaccine for plague, formulated by adsorption to alhydrogel, has been demonstrated to be immunogenic in the cynomolgus macaque in a clinically relevant dose-range and regimen.
72 citations
TL;DR: Two further putative clusters which encode capsular polysaccharide and LPS, both of which play roles in virulence, have been identified and are reported, demonstrating the immunological importance of the poly Saccharide clusters on the surface of B. pseudomallei.
Abstract: Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease of humans and animals. Gene clusters which encode capsular polysaccharide (type I O-PS) and LPS (type II O-PS), both of which play roles in virulence, have previously been identified. Here, the identification of two further putative clusters, type III O-PS and type IV O-PS, is reported. Mice challenged with type III O-PS or type IV O-PS mutants showed increased mean times to death (7.8 and 11.6 days) compared to those challenged with wild-type B. pseudomallei (3 days). To investigate the possible roles of polysaccharides in protection, mice were immunized with killed cells of wild-type B. pseudomallei or killed cells of B. pseudomallei with mutations in the O antigen, capsular polysaccharide, type III O-PS or type IV O-PS gene clusters. Immunization with all polysaccharide mutant strains resulted in delayed time to death compared to the naive controls, following challenge with wild-type B. pseudomallei strain K96243. However, immunization with killed polysaccharide mutant strains conferred different degrees of protection, demonstrating the immunological importance of the polysaccharide clusters on the surface of B. pseudomallei.
TL;DR: The most promising vaccine candidate, LolC, provided a greater level of protection when it was administered with immune-stimulating complexes complexed with CpG oligodeoxynucleotide 10103, demonstrating the potential utility of this protein as a vaccine antigen for melioidosis.
Abstract: Melioidosis is an emerging disease of humans in Southeast Asia and tropical Australia. The bacterium causing this disease, Burkholderia pseudomallei, is also considered a bioterrorism agent, and as yet there is no licensed vaccine for preventing B. pseudomallei infection. In this study, we evaluated selected proteins (LolC, PotF, and OppA) of the ATP-binding cassette systems of B. pseudomallei as candidate vaccine antigens. Nonmembrane regions of the B. pseudomallei proteins were expressed and purified from Escherichia coli and then evaluated as vaccine candidates in an established mouse model of B. pseudomallei infection. When delivered with the monophosphoryl lipid A-trehalose dicorynomycolate adjuvant, the proteins stimulated antigen-specific humoral and cellular immune responses. Immunization with LolC or PotF protein domains afforded significant protection against a subsequent challenge with B. pseudomallei. The most promising vaccine candidate, LolC, provided a greater level of protection when it was administered with immune-stimulating complexes complexed with CpG oligodeoxynucleotide 10103. Immunization with LolC also protected against a subsequent challenge with a heterologous strain of B. pseudomallei, demonstrating the potential utility of this protein as a vaccine antigen for melioidosis.
TL;DR: Oral immunization of A/J mice with Salmonella expressing full-length PA protected five of six mice against a challenge with 105 CFU of aerosolized B. anthracis STI spores, demonstrating for the first time the efficacy of an oral S. enterica-based vaccine against aerosolizer-based anthrax.
Abstract: Bacillus anthracis is the causative agent of anthrax, a disease that affects wildlife, livestock, and humans. Protection against anthrax is primarily afforded by immunity to the B. anthracis protective antigen (PA), particularly PA domains 4 and 1. To further the development of an orally delivered human vaccine for mass vaccination against anthrax, we produced Salmonella enterica serovar Typhimurium expressing full-length PA, PA domains 1 and 4, or PA domain 4 using codon-optimized PA DNA fused to the S. enterica serovar Typhi ClyA and under the control of the ompC promoter. Oral immunization of A/J mice with Salmonella expressing full-length PA protected five of six mice against a challenge with 10(5) CFU of aerosolized B. anthracis STI spores, whereas Salmonella expressing PA domains 1 and 4 provided only 25% protection (two of eight mice), and Salmonella expressing PA domain 4 or a Salmonella-only control afforded no measurable protection. However, a purified recombinant fusion protein of domains 1 and 4 provided 100% protection, and purified recombinant 4 provided protection in three of eight immunized mice. Thus, we demonstrate for the first time the efficacy of an oral S. enterica-based vaccine against aerosolized B. anthracis spores.
TL;DR: In this article, a standard search task was developed for assessing the effectiveness of arms and explosives search dogs following training and the results showed that the dogs' performance correlated significantly with the trainers' ratings of the dogs as taken throughout the training.
TL;DR: Comparative genomics and molecular typing methods suggest that the four different subspecies of F. tularensis are genetically distinct groups, and appear to have evolved by vertical descent from a common ancestor, probably F. Tularensis subspecies novicida.
Abstract: : The availability of the genome sequences of different strains of Francisella tularensis is having a major impact on a wide range of research projects, from understanding the biology of this organism to devising vaccines and diagnostics Comparative genomics and molecular typing methods suggest that the four different subspecies of F tularensis are genetically distinct groups Although there is a high degree of nucleotide identity between strains, there are numerous DNA rearrangements IS elements appear to have played a major role in these chromosomal rearrangements The different subspecies of F tularensis appear to have evolved by vertical descent from a common ancestor, probably F tularensis subspecies novicida Comparative genomic and proteomic studies have revealed possible reasons for the different virulence of different strains and a range of candidate virulence genes have been identified including those located on the Francisella pathogenicity island Proteomic studies have identified proteins which are produced at elevated levels in vivo, and proteins which are recognized by immune or convalescent sera These proteins might be exploited as components of vaccines or diagnostic systems
TL;DR: Medical countermeasures against ricin are urgently required and the strategy adopted has been first to understand the nature of the problem, in this case the inhalation toxicology of ricin, followed by the preparation of vaccine antigens.
Abstract: Ricin is a toxin and seed protein produced by the castor oil plant, Ricinus communis. The toxin is a dimeric protein consisting of an enzymic A chain and a B chain with lectin properties aiding the uptake of the whole molecule into cells. Ricin has been considered a possible military threat for several decades and is now also of some concern as a terrorist agent. The inhalation route is of primary concern in these situations, although previous attacks with ricin have used other approaches. Medical countermeasures against ricin are urgently required and the strategy adopted has been first to understand the nature of the problem, in this case the inhalation toxicology of ricin, followed by the preparation of vaccine antigens. Toxoided ricin and modified recombinant A chain components have been examined in terms of efficacy as potential vaccine candidates in protection of animal models against inhaled ricin, primarily in laboratories both in the United Kingdom and in the United States. One recombinant A chain vaccine has been taken through to clinical trials in the United States and should become commercially available in the next few years. Toxoided ricin has also been used as an antigen to prepare antitoxin antibodies for therapeutic treatment following poisoning. In this review, a synopsis of the inhalation toxicology of ricin and approaches to medical prophylaxis and therapy of poisoning is given, based on work conducted at our laboratory and at other research institutes.
TL;DR: Hydrophobic trioctylphosphine oxide-capped CdSe@ZnS quantum dots (QDs) are assembled on polyamine-coated microspheres in chloroform and encapsulated in an outer shell of silica nanoparticles functionalized with a specific recognition surface.
Abstract: This report describes a simple method for preparing encoded microspheres for use in multiplexed biological detection. In this method, hydrophobic trioctylphosphine oxide (TOPO)-capped CdSe@ZnS quantum dots (QDs) are assembled on polyamine-coated microspheres in chloroform and encapsulated in an outer shell of silica nanoparticles functionalized with a specific recognition surface. Because TOPO-capped QDs are assembled instead of their water-soluble equivalents, the microspheres are highly luminescent. The amount of QDs assembled depends only on the surface area of the substrate, and therefore, the photoluminescence intensity increased uniformly in proportion to the number of QD layers assembled. The outer shell of silica nanoparticles confers stability on the assembled QDs but has no effect on their photoluminescence because it is transparent to excitatory and emitted light. It was activated with aminosilane and functionalized with a recognition surface of protein antigens using disulfide exchange chemist...
TL;DR: The data presented here suggest that the Schu S4 laboratory strain is the most likely source of the European isolates of F. tularensis subsp.
Abstract: Background
Francisella tularensis causes tularaemia, a life-threatening zoonosis, and has potential as a biowarfare agent. F. tularensis subsp. tularensis, which causes the most severe form of tularaemia, is usually confined to North America. However, a handful of isolates from this subspecies was obtained in the 1980s from ticks and mites from Slovakia and Austria. Our aim was to uncover the origins of these enigmatic European isolates.
Methodology/Principal Findings
We determined the complete genome sequence of FSC198, a European isolate of F. tularensis subsp. tularensis, by whole-genome shotgun sequencing and compared it to that of the North American laboratory strain Schu S4. Apparent differences between the two genomes were resolved by re-sequencing discrepant loci in both strains. We found that the genome of FSC198 is almost identical to that of Schu S4, with only eight SNPs and three VNTR differences between the two sequences. Sequencing of these loci in two other European isolates of F. tularensis subsp. tularensis confirmed that all three European isolates are also closely related to, but distinct from Schu S4.
Conclusions/Significance
The data presented here suggest that the Schu S4 laboratory strain is the most likely source of the European isolates of F. tularensis subsp. tularensis and indicate that anthropogenic activities, such as movement of strains or animal vectors, account for the presence of these isolates in Europe. Given the highly pathogenic nature of this subspecies, the possibility that it has become established wild in the heartland of Europe carries significant public health implications.
TL;DR: The prospects for a killed whole-cell subunit of live attenuated vaccine are reviewed and a rationally attenuated mutant seems the most likely route to a new tularaemia vaccine.
Abstract: Francisella tularensis is the causative agent of tularaemia, a disease which occurs naturally in some countries in the northern hemisphere. Recently, there has been a high level of interest in devising vaccines against the bacterium because of the potential for it to be used as a bioterrorism agent. Previous human volunteer studies have shown that a strain of F. tularensis [the live vaccine strain (LVS)] that has been attenuated by laboratory passage is effective in humans as a vaccine against airborne disease. However, for a variety of reasons it seems unlikely that the LVS strain will be licensed for use in humans. Against this background there is an effort to devise a licensable vaccine against tularaemia. The prospects for a killed whole-cell subunit of live attenuated vaccine are reviewed. A rationally attenuated mutant seems the most likely route to a new tularaemia vaccine.
TL;DR: It is suggested that purine auxotrophs of F. tularensis should be further evaluated as live attenuated vaccines against tularemia, but that differential effects are seen depending on which step in the biosynthetic pathway is inactivated.
TL;DR: There is little conclusive evidence that primary ocular blast injury occurs in survivors of explosions and if it does occur, it is more likely to be at high overpressures that will produce life-threatening injuries.
Abstract: Objectives Eye injuries are relatively common following detonations. The majority of these are caused by secondary fragments. Primary blast injury to the eye (from the air-blast alone) has been described historically, but the differentiation of air-blast and fragment aetiologies in the reports is not clear. The aim of this review is to consider the evidence in the literature for true primary blast injury to the eye. Methods A literature review using Medline, Pub-med and Web of Knowledge databases. Conclusions Overall, there is little conclusive evidence that primary ocular blast injury occurs in survivors of explosions. However, some case reports do surmise its occurrence and it cannot be unequivocally ruled out. If it does occur, it is more likely to be at high overpressures that will produce life-threatening injuries. The development of enhanced blast weapons may result in an increased incidence. At present however, the most severe and damaging threat to the eyes from blast remains the impact of fragments and debris.
TL;DR: In this paper, a combination of layer-by-layer self-assembly and magnetic separation has been used to encode magnetic microspheres with multiple colours of photoluminescent semiconductor quantum dots (QDs).
Abstract: A combination of layer-by-layer (LBL) self-assembly and magnetic separation has been used to encode magnetic microspheres with multiple colours of photoluminescent semiconductor quantum dots (QDs). Magnetic separation increased the speed of the LBL process and led to high yields of encoded microspheres. This is important because it allows the full potential of QDs to be harnessed for optically encoded microspheres. The assembly process was investigated using fluorescence microscopy, transmission electron microscopy (TEM) and microelectrophoresis. The same assembly process was repeated on planar surfaces and investigated using atomic force microscopy (AFM) and UV/vis spectroscopy. Three sets of microspheres with different spectral codes were combined to form a suspension array that was used to screen for three different types of explosive in the same sample. Results were analyzed with a fluorescence microscope that decoded the microspheres and detected fluorescent reporter molecules bound to their surface. The results allowed individual explosives and mixtures of explosives to be detected in multiplexed immunoassays.
TL;DR: The limited statistical analysis in this study supports the conclusion that coagulopathy is present in a significant proportion of severely-injured patients by the time they arrive at hospital.
Abstract: Prevalence of coagulopathy in trauma According to the British Committee for Standards in Haematology and the American College of Pathologists, prolongation of the activated partial thromboplastin time (APTT) and prothrombin time (PT) to 1.5 times the mean normal value indicates a coagulopathy requiring blood product replacement [1-3]. A number of studies have indicated that coagulopathy is common after severe trauma and that it results from a number of causes including metabolic acidosis, hypothermia, dilution of coagulation factors by resuscitation fluids and consumption of coagulation factors [4-10]. Coagulopathy is especially associated with some forms of injury, e.g. brain injury, because of the release of tissue thromboplastins from damaged brain matter [11; 12]. A UK civilian study by Brohi et al [13], using the definitions given above, clearly demonstrated that major trauma patients (Injury Severity Score, ISS >15) can present at hospital with a coagulopathy: 24% of 1088 trauma patients (median ISS 20) analyzed on arrival at the Emergency Department (ED) were coagulopathic. The majority (75%) of patients had suffered blunt trauma and the median time from injury to hospital was 73 minutes; this is compared to 7.6% blunt force (motor vehicle crash, fall, assault, crush) in 876 patients on the UK military Joint Theatre Trauma Registry (01 April 2006 to 30 September 2007, OP HERRICK and OP TELIC only), and a median injury to ED handover time of 97 minutes for UK military priority 1 casualties [14]. The incidence of coagulopathy increased with severity of injury (assessed by ISS), independent of the volume of pre-hospital resuscitation fluid (reliably recorded by a physician). The authors comment that the patients had received minimal pre-hospital fluid resuscitation (median values of 500 ml crystalloid or 1000 ml colloid) and that the development of coagulopathy in these patients was unrelated to the volume or type of intravenous fluid given. A second survey [15] based on 8724 severely injured patients (96% blunt injuries) from the German Trauma Registry Database confirms the presence of coagulopathy in 34% of all severely injured patients arriving in the Emergency Department. This study used a similar definition of coagulopathy to that employed by Brohi et al [13] and identified a similar time to hospital. The presence of coagulopathy was positively associated with the volume of pre-hospital fluid, injury severity and delay between injury and arrival at hospital [15]. Even in patients with minimal pre-hospital resuscitation, coagulopathy was present in 10% of cases [15]. Despite the limited statistical analysis in this study it supports the conclusion that coagulopathy is present in a significant proportion of severely-injured patients by the time they arrive at hospital. Early coagulopathy was also reported by MacLeod et al [16] in a retrospective analysis of 7638 trauma patients admitted to a Level 1 Trauma Centre between Jan 1995 and Dec 2000, although as a group these patients were less severely injured (median ISS 9) than those described by Brohi et al [13]. Additionally, MacLeod et al [16] were unable to account for medication that might have contributed to the coagulopathy, for example warfarin treatment or pre-hospital fluid administration. A number of other smaller studies [17; 18] and anecdotal comments [19]] have also documented coagulopathy in trauma patients on arrival at hospital. Furthermore, early coagulopathy is associated with increased morbidity and mortality [13; 15; 16; 18]. Although it is always a concern that studies with negative conclusions are less likely to be published than those with a positive conclusion, the collective evidence strongly suggests that a proportion of severely injured patients are already coagulopathic by the time they arrive in the Emergency Department and the remainder are at high risk of rapidly developing a coagulopathy. Clearly the true incidence of coagulopathy will depend on the definition adopted. There is evidence that bleeding time and thromboelastographic measurements are better indicators of dilutional and hypothermia induced coagulopathy [20]. Using this methodology the true incidence of coagulopathy associated with major trauma may well be significantly higher than reported.
TL;DR: Differences in the number and types of encoded ABC systems in belonging to these organisms have been identified and have the potential to be exploited for improved clinical identification of these organisms as well as in the development of new vaccines and therapeutics targeted against the diseases caused by these organisms.
Abstract: Background
ATP binding cassette (ABC) systems are responsible for the import and export of a wide variety of molecules across cell membranes and comprise one of largest protein superfamilies found in prokarya, eukarya and archea. ABC systems play important roles in bacterial lifestyle, virulence and survival. In this study, an inventory of the ABC systems of Burkholderia pseudomallei strain K96243 and Burkholderia mallei strain ATCC 23344 has been compiled using bioinformatic techniques.
TL;DR: In the absence of effective antiviral drugs and vaccines to combat VEEV infection, these siRNAs offer a potential new therapeutic approach but, as with all antimicrobial agents, caution needs to be exercised with respect to the generation of resistance.
TL;DR: To eliminate interference from additional protein sequences, LcrVs without affinity tags from Y. pestis and Y. enterocolitica O:8 were produced and LcrVO:8 was much more potent in TLR2-activity than Y. pests LcrV, which might explain why TLR 2-deficient mice are not more resistant than wild-type mice in a bubonic plague model.
TL;DR: Evaluating UK Service deaths in the first year of operations in Helmand Province, Afghanistan, comparing hostile action wounding mechanisms, patterns, salvageability and preventability with UK Service death in Iraq for the same period is evaluated.
Abstract: Email: Prof.ADMEM@rcdm.bham.ac.uk Introduction Details of all UK military deaths on operations are collected from clinical notes, post mortem reports and incident reports and are held on the UK Joint Theatre Trauma Registry, maintained by the Academic Department of Military Emergency Medicine (ADMEM) at the Royal Centre for Defence Medicine (RCDM). Analysis of these deaths is used to determine emerging injury patterns, to monitor clinical effectiveness, and to inform personal and vehicular protective systems. This paper evaluates UK Service deaths in the first year of operations in Helmand Province, Afghanistan, comparing hostile action wounding mechanisms, patterns, salvageability and preventability with UK Service deaths in Iraq for the same period.
TL;DR: Urine, from human volunteers with no known exposure to sulphur mustard, contained detectable but very low concentrations ofThiodiglycol, consistent with previous observations using different methodologies, and sulphoxide was the major excretion product of the two metabolites.
TL;DR: Evidence for a lack of arrhythmogenic action of the M26 and X26 TASER devices is provided.
Abstract: Increasing use by law enforcement agencies of the M26 and X26 TASER electrical incapacitation devices has raised concerns about the arrhythmogenic potential of these weapons. Using a numerical phantom constructed from medical images of the human body in which the material properties of the tissues are represented, computational electromagnetic modelling has been used to predict the currents arising at the heart following injection of M26 and X26 waveforms at the anterior surface of the chest (with one TASER 'barb' directly overlying the ventricles). The modelling indicated that the peak absolute current densities at the ventricles were 0.66 and 0.11 mA mm−2 for the M26 and X26 waveforms, respectively. When applied during the vulnerable period to the ventricular epicardial surface of guinea-pig isolated hearts, the M26 and X26 waveforms induced ectopic beats, but only at current densities greater than 60-fold those predicted by the modelling. When applied to the ventricles in trains designed to mimic the discharge patterns of the TASER devices, neither waveform induced ventricular fibrillation at peak currents >70-fold (for the M26 waveform) and >240-fold (for the X26) higher than the modelled current densities. This study provides evidence for a lack of arrhythmogenic action of the M26 and X26 TASER devices. For more information on this article, see medicalphysicsweb.org