The risk of fragment penetrating injury to the heart

Injury due to the penetration of fragments into parts of the body has been the major cause of morbidity and mortality after an explosion. Penetrating injuries into the heart present very high mortality, yet the risk associated with such injuries has not been quantified. Quantifying this risk is key in the design of personal protection and the design of infrastructure. This study is the first quantitative assessment of cardiac penetrating injuries from energised fragments. Typical fragments (5-mm sphere, 0.78-g right-circular cylinder and 1.1-g chisel-nosed cylinder) were accelerated to a range of target striking velocities using a bespoke gas-gun system and impacted ventricular and atrial walls of lamb hearts. The severity of injury was shown to not depend on location (ventricular or atrial wall). The striking velocity with 50% probability of critical injury (Abbreviated Injury Scale (AIS) 5 score) ranged between 31 and 36 m/s across all 3 fragments used. These findings can help directly in reducing morbidity and mortality from explosive events as they can be implemented readily into models that aim to predict casualties in an explosive event, inform protocols for first responders, and improve design of infrastructure and personal protective equipment

Lysophosphatidylcholine in phospholipase A(2)-modified LDL triggers secretion of angiopoietin 2

Background and aims: Secretory phospholipase A(2) (PLA(2)) hydrolyzes LDL phospholipids generating modified LDL particles (PLA(2)-LDL) with increased atherogenic properties. Exocytosis of Weibel-Palade bodies (WPB) releases angiopoietin 2 (Ang2) and externalizes P-selectin, which both play important roles in vascular inflammation. Here, we investigated the effects of PLA(2)-LDL on exocytosis of WPBs. Methods: Human coronary artery endothelial cells (HCAECs) were stimulated with PLA(2)-LDL, and its uptake and effect on Ang2 release, leukocyte adhesion, and intracellular calcium levels were measured. The effects of PLA(2)-LDL on Ang2 release and WPB exocytosis were measured in and ex vivo in mice. Results: Exposure of HCAECs to PLA(2)-LDL triggered Ang2 secretion and promoted leukocyte-HCAEC interaction. Lysophosphatidylcholine was identified as a critical component of PLA(2)-LDL regulating the WPB exocytosis, which was mediated by cell-surface proteoglycans, phospholipase C, intracellular calcium, and cytoskeletal remodeling. PLA(2)-LDL also induced murine endothelial WPB exocytosis in blood vessels in and ex vivo, as evidenced by secretion of Ang2 in vivo, P-selectin translocation to plasma membrane in intact endothelial cells in thoracic artery and tracheal vessels, and reduced Ang2 staining in tracheal endothelial cells. Finally, in contrast to normal human coronary arteries, in which Ang2 was present only in the endothelial layer, at sites of advanced atherosclerotic lesions, Ang2 was detected also in the intima, media, and adventitia. Conclusions: Our studies reveal PLA(2)-LDL as a potent agonist of endothelial WPB exocytosis, resulting in increased secretion of Ang2 and translocation of P-selectin. The results provide mechanistic insight into PLA(2)-LDL-dependent promotion of vascular inflammation and atherosclerosis.Peer reviewe

Implementation of Web-Based Respondent-Driven Sampling among Men who Have Sex with Men in Vietnam

Objective: Lack of representative data about hidden groups, like men who have sex with men (MSM), hinders an evidence-based response to the HIV epidemics. Respondent-driven sampling (RDS) was developed to overcome sampling challenges in studies of populations like MSM for which sampling frames are absent. Internet-based RDS (webRDS) can potentially circumvent limitations of the original RDS method. We aimed to implement and evaluate webRDS among a hidden population. Methods and Design: This cross-sectional study took place 18 February to 12 April, 2011 among MSM in Vietnam. Inclusion criteria were men, aged 18 and above, who had ever had sex with another man and were living in Vietnam. Participants were invited by an MSM friend, logged in, and answered a survey. Participants could recruit up to four MSM friends. We evaluated the system by its success in generating sustained recruitment and the degree to which the sample compositions stabilized with increasing sample size. Results: Twenty starting participants generated 676 participants over 24 recruitment waves. Analyses did not show evidence of bias due to ineligible participation. Estimated mean age was 22 year and 82% came from the two large metropolitan areas. 32 out of 63 provinces were represented. The median number of sexual partners during the last six months was two. The sample composition stabilized well for 16 out of 17 variables. Conclusion: Results indicate that webRDS could be implemented at a low cost among Internet-using MSM in Vietnam. WebRDS may be a promising method for sampling of Internet-using MSM and other hidden groups. Key words: Respondent-driven sampling, Online sampling, Men who have sex with men, Vietnam, Sexual risk behavio

Effect of Systematically Tuning Conjugated Donor Polymer Lowest Unoccupied Molecular Orbital Levels via Cyano Substitution on Organic Photovoltaic Device Performance

We report a systematic study into the effects of cyano substitution on the electron accepting ability of the common acceptor 4,7-bis(thiophen-2-yl)-2,1,3-benzothiadiazole (DTBT). We describe the synthesis of DTBT monomers with either 0, 1, or 2 cyano groups on the BT unit and their corresponding copolymers with the electron rich donor dithienogermole (DTG). The presence of the cyano group is found to have a strong influence on the optoelectronic properties of the resulting donor–acceptor polymers, with the optical band gap red-shifting by approximately 0.15 eV per cyano substituent. We find that the polymer electron affinity is significantly increased by ∼0.25 eV upon addition of each cyano group, while the ionization potential is less strongly affected, increasing by less than 0.1 eV per cyano substituent. In organic photovoltaic (OPV) devices power conversion efficiencies (PCE) are almost doubled from around 3.5% for the unsubstituted BT polymer to over 6.5% for the monocyano substituted BT polymer. However, the PCE drops to less than 1% for the dicyano substituted BT polymer. These differences are mainly related to differences in the photocurrent, which varies by 1 order of magnitude between the best (1CN) and worst devices (2CN). The origin of this variation in the photocurrent was investigated by studying the charge generation properties of the photoactive polymer–fullerene blends using fluorescence and transient absorption spectroscopic techniques. These measurements revealed that the improved photocurrent of 1CN in comparison to 0CN was due to improved light harvesting properties while maintaining a high exciton dissociation yield. The addition of one cyano group to the BT unit optimized the position of the polymer LUMO level closer to that of the electron acceptor PC71BM, such that the polymer’s light harvesting properties were improved without sacrificing either the exciton dissociation yield or device VOC. We also identify that the drop in performance for the 2CN polymer is caused by very limited yields of electron transfer from the polymer to the fullerene, likely caused by poor orbital energy level alignment with the fullerene acceptor (PC71BM). This work highlights the impact that small changes in chemical structure can have on the optoelectronic and device properties of semiconducting polymer. In particular this work highlights the effect of LUMO–LUMO offset on the excited state dynamics of polymer–fullerene blends

The critical role of a backing material in assessing the performance of soft ballistic protection

Penetrating trauma by energised fragments is the most common injury from an explosive event. Fragment penetrations to the truncal region can result in lethal haemorrhage. Personal armour is used to mitigate ballistic threats; it comprises hard armour to protect from high-velocity bullets and soft armour to protect against energised fragments and other ballistic threats (such as from a hand gun) with low impact velocities. Current testing standards for soft armour do not focus on realistic boundary conditions, and a backing material is not always recommended. This study provides a comprehensive set of evidence to support the inclusion of a backing used in testing of soft body armour. Experiments were performed with a gas-gun system using fragment-simulating projectiles (FSPs) of different shapes and sizes to impact on a woven aramid and a knitted high-performance polyethylene ballistic fabric, with and without the ballistic gelatine soft tissue simulant as the backing material. The results showed statistically significant differences in the impact velocities at 50% risk (V50) of fabric perforation across all test configurations when the gelatine backing was used. Furthermore, the backing material enabled the collection of injury-related metrics such as V50 of tissue-simulant penetrations as well as depth of penetration against impact velocity. The normalised energy absorbed by the fabric could also be calculated when the backing material was present. This study confirms that a backing material is essential, particularly when assessing the performance of single layer fabrics against FSPs of low mass. It also demonstrates the additional benefits provided by the backing for predicting injury outcomes

Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: an inter-laboratory study.

Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a 'one-stop' test for epidemiological and predictive AST results. Few published comparisons exist for the myriad analytical pipelines used for predicting AMR. To address this, we performed an inter-laboratory study providing sets of participating researchers with identical short-read WGS data from clinical isolates, allowing us to assess the reproducibility of the bioinformatic prediction of AMR between participants, and identify problem cases and factors that lead to discordant results. We produced ten WGS datasets of varying quality from cultured carbapenem-resistant organisms obtained from clinical samples sequenced on either an Illumina NextSeq or HiSeq instrument. Nine participating teams ('participants') were provided these sequence data without any other contextual information. Each participant used their choice of pipeline to determine the species, the presence of resistance-associated genes, and to predict susceptibility or resistance to amikacin, gentamicin, ciprofloxacin and cefotaxime. We found participants predicted different numbers of AMR-associated genes and different gene variants from the same clinical samples. The quality of the sequence data, choice of bioinformatic pipeline and interpretation of the results all contributed to discordance between participants. Although much of the inaccurate gene variant annotation did not affect genotypic resistance predictions, we observed low specificity when compared to phenotypic AST results, but this improved in samples with higher read depths. Had the results been used to predict AST and guide treatment, a different antibiotic would have been recommended for each isolate by at least one participant. These challenges, at the final analytical stage of using WGS to predict AMR, suggest the need for refinements when using this technology in clinical settings. Comprehensive public resistance sequence databases, full recommendations on sequence data quality and standardization in the comparisons between genotype and resistance phenotypes will all play a fundamental role in the successful implementation of AST prediction using WGS in clinical microbiology laboratories

Anonymous Single-Sign-On for n designated services with traceability

Anonymous Single-Sign-On authentication schemes have been proposed to allow users to access a service protected by a verifier without revealing their identity which has become more important due to the introduction of strong privacy regulations. In this paper we describe a new approach whereby anonymous authentication to different verifiers is achieved via authorisation tags and pseudonyms. The particular innovation of our scheme is authentication can only occur between a user and its designated verifier for a service, and the verification cannot be performed by any other verifier. The benefit of this authentication approach is that it prevents information leakage of a user's service access information, even if the verifiers for these services collude which each other. Our scheme also supports a trusted third party who is authorised to de-anonymise the user and reveal her whole services access information if required. Furthermore, our scheme is lightweight because it does not rely on attribute or policy-based signature schemes to enable access to multiple services. The scheme's security model is given together with a security proof, an implementation and a performance evaluation.Comment: 3

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Protective clothing reduces lower limb injury severity against propelled sand debris in a laboratory setting

The contribution of energised environmental debris to injury patterns of the blast casualty is not known. The extent to which personal protective equipment (PPE) limits the injuries sustained by energised environmental debris following an explosive event is also not known. In this study, a cadaveric model exposed to a gas-gun mediated sand blast was utilised which reproduced soft-tissue injuries representative of those seen clinically following blast. Mean sand velocity across experiments was 506 ± 80 ms−1. Cadaveric samples wearing standard-issue PPE were shown to have a reduced injury severity to sand blast compared to control: a statistically significant reduction was seen in the total surface area (143 mm2 vs. 658 mm2, p = 0.004) and depth of injuries (0 vs. 23 deep injuries, odds ratio = 0.0074, 95% confidence intervals 0.0004–0.1379). This study is the first to recreate wounds from propelled sand in a human cadaveric model. These findings implicate environmental debris, such as sand ejected from a blast event, as a critical mechanism of injury in the blast casualty. Tier 1 pelvic PPE was shown to reduce markedly the severity of injury. This injury mechanism should be a key focus of future research and mitigation strategies

Lung Clearance Index (LCI) is Stable in Most Primary Ciliary Dyskinesia (PCD) Patients Managed in a Specialist Centre:a Pilot Study

Primary ciliary dyskinesia is a condition in which abnormal cilia structure or function leads to reduced mucociliary clearance and obstructive lung disease. Twenty-nine patients had lung clearance index (LCI) measured in 2009 and we attempted to perform a 5-year follow-up. Only 12 patients could be re-recruited, but in this small group LCI was stable over the 5 years, which confirms previous data showing that spirometry is also stable in these patients over the medium term. The two patients with the highest LCI in 2009 had since died, despite one having relatively preserved spirometry at the time. These data may be used to inform sample size calculations of future studies