Defence Science and Technology Laboratory

About: Defence Science and Technology Laboratory is a government organization based out in Salisbury, United Kingdom. It is known for research contribution in the topics: Burkholderia pseudomallei & Francisella tularensis. The organization has 926 authors who have published 1242 publications receiving 30091 citations. The organization is also known as: Dstl & [dstl].

Evaluation of Prehospital Blood Products to Attenuate Acute Coagulopathy of Trauma in a Model of Severe Injury and Shock in Anesthetized Pigs.

Abstract: Acute trauma coagulopathy (ATC) is seen in 30% to 40% of severely injured casualties. Early use of blood products attenuates ATC, but the timing for optimal effect is unknown. Emergent clinical practice has started prehospital deployment of blood products (combined packed red blood cells and fresh frozen plasma [PRBCs:FFP], and alternatively PRBCs alone), but this is associated with significant logistical burden and some clinical risk. It is therefore imperative to establish whether prehospital use of blood products is likely to confer benefit. This study compared the potential impact of prehospital resuscitation with (PRBCs:FFP 1:1 ratio) versus PRBCs alone versus 0.9% saline (standard of care) in a model of severe injury. Twenty-four terminally anesthetised Large White pigs received controlled soft tissue injury and controlled hemorrhage (35% blood volume) followed by a 30-min shock phase. The animals were allocated randomly to one of three treatment groups during a 60-min prehospital evacuation phase: hypotensive resuscitation (target systolic arterial pressure 80 mmHg) using either 0.9% saline (group 1, n = 9), PRBCs:FFP (group 2, n = 9), or PRBCs alone (group 3, n = 6). Following this phase, an in-hospital phase involving resuscitation to a normotensive target (110 mmHg systolic arterial blood pressure) using PRBCs:FFP was performed in all groups. There was no mortality in any group. A coagulopathy developed in group 1 (significant increase in clot initiation and dynamics shown by TEG [thromboelastography] R and K times) that persisted for 60 to 90 min into the in-hospital phase. The coagulopathy was significantly attenuated in groups 2 and 3 (P = 0.025 R time and P = 0.035 K time), which were not significantly different from each other. Finally, the volumes of resuscitation fluid required was significantly greater in group 1 compared with groups 2 and 3 (P = 0.0067) (2.8 ± 0.3 vs. 1.9 ± 0.2 and 1.8 ± 0.3 L, respectively). This difference was principally due to a greater volume of saline used in group 1 (P = 0.001). Prehospital PRBCs:FFP or PRBCs alone may therefore attenuate ATC. Furthermore, the amount of crystalloid may be reduced with potential benefit of reducing the extravasation effect and later tissue edema.

Evaluation of the Biofire FilmArray BioThreat-E Test (v2.5) for Rapid Identification of Ebola Virus Disease in Heat-Treated Blood Samples Obtained in Sierra Leone and the United Kingdom

Abstract: Rapid Ebola virus (EBOV) detection is crucial for appropriate patient management and care. The performance of the FilmArray BioThreat-E test (v2.5) using whole-blood samples was evaluated in Sierra Leone and the United Kingdom and was compared with results generated by a real-time Ebola Zaire PCR reference method. Samples were tested in diagnostic laboratories upon availability, included successive samples from individual patients, and were heat treated to facilitate EBOV inactivation prior to PCR. The BioThreat-E test had a sensitivity of 84% (confidence interval [CI], 64% to 95%) and a specificity of 89% (CI, 73% to 97%) in Sierra Leone (n = 60; 44 patients) and a sensitivity of 75% (CI, 19% to 99%) and a specificity of 100% (CI, 97% to 100%) in the United Kingdom (n = 108; 70 patients) compared to the reference real-time PCR. Statistical analysis (Fisher's exact test) indicated there was no significant difference between the methods at the 99% confidence level in either country. In 9 discrepant results (5 real-time PCR positives and BioThreat-E test negatives and 4 real-time PCR negatives and BioThreat-E test positives), the majority (n = 8) were obtained from samples with an observed or probable low viral load. The FilmArray BioThreat-E test (v2.5) therefore provides an attractive option for laboratories (either in austere field settings or in countries with an advanced technological infrastructure) which do not routinely offer an EBOV diagnostic capability.

The type IV pilin, PilA, is required for full virulence of Francisella tularensis subspecies tularensis.

Abstract: Background All four Francisella tularensis subspecies possess gene clusters with potential to express type IV pili (Tfp). These clusters include putative pilin genes, as well as pilB, pilC and pilQ, required for secretion and assembly of Tfp. A hallmark of Tfp is the ability to retract the pilus upon surface contact, a property mediated by the ATPase PilT. Interestingly, out of the two major human pathogenic subspecies only the highly virulent type A strains have a functional pilT gene.

Inferring missing links in partially observed social networks

Abstract: Determining the pattern of links within a large social network is often problematic due to the labour-intensive nature of the data collection and analysis process With constrained data collection capabilities it is often only possible to either make detailed observations of a limited number of individuals in the network, or to make fewer observations of a larger number of people Previously we have shown how detailed observation of a small network can be used, which infer where in the network previously unconnected individuals are likely to fit, thereby attempting to predict network growth as new people are considered for inclusion Here, by contrast, we show how social network topology can be inferred following a limited observation of a large network Essentially the issue is one of inferring the presence of links that are missed during a constrained data collection campaign on the network It is particularly difficult to infer network structures for those organizations that actively seek to remain covert and undetected However, it is often very useful to know if two given individuals are likely to be connected even though limited surveillance effort yields no evidence of a link Specifically, we show how a statistical inference technique can be used to successfully predict the existence of links that are missed during network sampling The procedure is demonstrated using network data obtained from open source publications

Global Map of Growth-Regulated Gene Expression in Burkholderia pseudomallei, the Causative Agent of Melioidosis

Abstract: Many microbial pathogens express specific virulence traits at distinct growth phases. To understand the molecular pathways linking bacterial growth to pathogenicity, we have characterized the growth transcriptome of Burkholderia pseudomallei, the causative agent of melioidosis. Using a fine-scale sampling approach, we found approximately 17% of all B. pseudomallei genes displaying regulated expression during growth in rich medium, occurring as broad waves of functionally coherent gene expression tightly associated with distinct growth phases and transition points. We observed regulation of virulence genes across all growth phases and identified serC as a potentially new virulence factor by virtue of its coexpression with other early-phase virulence genes. serC-disrupted B. pseudomallei strains were serine auxotrophs and in mouse infection assays exhibited a dramatic attenuation of virulence compared to wild-type B. pseudomallei. Immunization of mice with serC-disrupted B. pseudomallei also conferred protection against subsequent challenges with different wild-type B. pseudomallei strains. At a genomic level, early-phase genes were preferentially localized on chromosome 1, while stationary-phase genes were significantly biased towards chromosome 2. We detected a significant level of chromosomally clustered gene expression, allowing us to predict ∼100 potential operons in the B. pseudomallei genome. We computationally and experimentally validated these operons by showing that genes in these regions are preferentially transcribed in the same 5′→3′ direction, possess significantly shorter intergenic lengths than the overall genome, and are expressed as a common mRNA transcript. The availability of this transcriptome map provides an important resource for understanding the transcriptional architecture of B. pseudomallei.