Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “hemorrhage”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3

Pathogenesis of Chapare Virus in Cynomolgus Macaques

Chapare virus (CHAPV) is an emerging New World arenavirus that is the causative agent of Chapare hemorrhagic fever (CHHF) responsible for recent outbreaks with alarmingly high case fatality rates in Bolivia near the Brazilian border. Here, we describe a nonhuman primate (NHP) model of CHHF infection which represents an essential tool to understand this emerging biological threat agent. Cynomolgus macaques challenged intravenously with CHAPV develop clinical disease, which recapitulates several key features of human CHHF. All subjects lost weight and had clinical scores following CHAPV challenge. Notably, one of four NHPs developed lethal disease with viral hepatitis and hemorrhagic features. Clinical chemistry and hematology revealed leukopenia, anemia, thrombocytopenia, and increased transaminase levels. In all four subjects, viremia was detectable for the first week following challenge and viral RNA was detectable in serum and many tissues persisting 35 days-post challenge. Several medical countermeasures (MCM) have efficacy against CHAPV infection in vitro, but the current model for MCM testing and approval of new drugs is reliant on the availability of animal models. This work lays the foundation for future CHHF MCM development.

60 APPLIED LIFE SCIENCES↗

Supervisory Algorithm for Autonomous Hemodynamic Management Systems

Future military conflicts will require new solutions to manage combat casualties. The use of automated medical systems can potentially address this need by streamlining and augmenting the delivery of medical care in both emergency and combat trauma environments. However, in many situations, these systems may need to operate in conjunction with other autonomous and semi-autonomous devices. Management of complex patients may require multiple automated systems operating simultaneously and potentially competing with each other. Supervisory controllers capable of harmonizing multiple closed-loop systems are thus essential before multiple automated medical systems can be deployed in managing complex medical situations. The objective for this study was to develop a Supervisory Algorithm for Casualty Management (SACM) that manages decisions and interplay between two automated systems designed for management of hemorrhage control and resuscitation: an automatic extremity tourniquet system and an adaptive resuscitation controller. SACM monitors the required physiological inputs for both systems and synchronizes each respective system as needed. We present a series of trauma experiments carried out in a physiologically relevant benchtop circulatory system in which SACM must recognize extremity or internal hemorrhage, activate the corresponding algorithm to apply a tourniquet, and then resuscitate back to the target pressure setpoint. SACM continues monitoring after the initial stabilization so that additional medical changes can be quickly identified and addressed, essential to extending automation algorithms past initial trauma resuscitation into extended monitoring. Overall, SACM is an important step in transitioning automated medical systems into emergency and combat trauma situations. Future work will address further interplay between these systems and integrate additional medical systems.

42 ENGINEERING↗

Development and Characterization of a Self-Tightening Tourniquet System

Uncontrolled hemorrhage remains a leading cause of death in both emergency and military medicine. Tourniquets are essential to stopping hemorrhage in these scenarios, but they suffer from subjective, inconsistent application. Here, we demonstrate how tourniquet application can be automated using sensors and computer algorithms. The auto-tourniquet self-tightens until blood pressure oscillations are no longer registered by the pressure sensor connected to the pneumatic pressure cuff. The auto-tourniquet’s performance in stopping the bleed was comparable to manual tourniquet application, but the time required to fully occlude the bleed was longer. Application of the tourniquet was significantly smoother, and less variable, for the automatic tourniquet compared to manual tourniquet application. This proof-of-concept study highlights how automated tourniquets can be integrated with sensors to provide a much more consistent application and use compared to manual application, even in controlled, low stress testing conditions. Future work will investigate different sensors and tourniquets to improve the application time and repeatability.

Vega, Saul J.↗

Funduscopic alterations in the rhesus monkey induced by exposure to heavy ions /0+8/ 250 MeV/nucleon

A heavy-ion, high-energy beam has been extracted from the Lawrence Radiation Laboratory Bevatron, making controlled exposure of biological systems feasible, and a series of experiments have been undertaken to determine the possible deleterious effects of such irradiation upon the primate retina. The left eyes of 54 rhesus monkeys have been exposed to accelerated 0+8 (250 MeV/nucleon). Beam flux ranged from 1.3 x 10 to the 7th particles/ sq cm (171 rads) to 5.9 x 10 to the 8th particles/sq cm (7740 rads). Fundus photography was performed immediately prior to and immediately following exposure, at 24 to 48 hours postexposure and at 1, 2, and 5 weeks postexposure. Punctate hemorrhages of the retina were visible at 1.3 x 10 to the 7th particles/sq cm (171 rads), the lowest exposure level utilized in this study. Acute radiation retinopathy, consisting of geographic retinal hemorrhage and ischemic necrosis of the retina, was not seen until total flux reached 7.7 x 10 to the 7th particles/sq cm (1000 rads).

Beckman, F. N.↗

Effects of heavy ion radiation on the brain vascular system and embryonic development

The present investigation is concerned with the effects of heavy-ion radiation on the vascular system and the embryonic development, taking into account the results of experiments with neonatal rats and mouse embryos. It is found that heavy ions can be highly effective in producing brain hemorrhages and in causing body deformities. Attention is given to aspects of methodology, the induction of brain hemorrhages by X-rays and heavy ions, and the effect of iron particles on embryonic development. Reported results suggest that high linear energy transfer (LET) heavy ions can be very effective in producing developmental abnormalities.

Yang, T. C.↗

Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma

PURPOSE: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. METHODS AND MATERIALS: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. RESULTS: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. CONCLUSION: The development of NVG after helium-ion irradiation is correlated to the amount of lens, anterior chamber in the treatment field, tumor height, proximity to the fovea, history of diabetes, and the development of vitreous hemorrhage. Although the influence of the higher LET deposition of helium-ions is unclear, this study suggests that by reducing the dose to the anterior segment of the eye may reduce the NVG complications. Based on this retrospective analysis of LBNL patients, we have implemented techniques to reduce the amount of the anterior segment receiving a high dose in our new series of patients treated with protons using the cyclotron at the UC Davis Crocker Nuclear Laboratory (CNL).

NASA Discipline Radiation Health↗

Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure < 70 mmHg, head trauma, and penetrating injury requiring surgery. HSD and HSS have received regulatory approval in 14 and 3 countries, respectively, with 81,000+ units sold. The primary reported use was head injury and trauma resuscitation. Complications and reported adverse events are surprisingly rare and not significantly different from other solutions.HBOCs are potent volume expanders in addition to oxygen carriers with volume expansion greater than standard colloids. Several investigators have evaluated small volume hyperoncotic HBOCs or HS-HBOC formulations for hypotensive and normotensive resuscitation in animals. A consistent finding in resuscitation with HBOCs is depressed cardiac output. There is some evidence that HBOCs more efficiently unload oxygen from plasma hemoglobin as well as facilitate RBC unloading. We analyzed one volunteer study, 15 intraoperative trials, and 3 trauma studies using HBOCs. Perioperative studies generally suggest ability to deliver oxygen, but one trauma trial using HBOCs (HemAssist) for treatment of trauma resulted in a dramatic increase in mortality, while an intraoperative trauma study using Polyheme demonstrated reductions in blood use and lower mortality compared to historic controls of patients refusing blood. Transfusion reductions with HBOC use have been modest. Two HBOCs (Hemopure and Polyheme) are now in new or planned large-scale multicenter prehospital trials of trauma treatment. A new implementation of small volume resuscitation is closed-loop resuscitation (CLR), which employs microprocessors to titrate just enough fluid to reach a physiologic target . Animal studies suggest less risk of rebleeding in uncontrolled hemorrhage and a reduction in fluid needs with CLR. The first clinical application of CLR was treatment of burn shock and the US Army. Conclusions: Independently sponsored civilian trauma trials and clinical evaluations in operational combat conditions of different small volume strategies are warranted.

Kramer, George C.↗

Filovirus Research: The Need for an Integrated Approach in Time and Space

The episodic appearance of Ebola virus (EBOV) and Marburg virus (MARV) across central Africa over the last 15 years not only underscores the importance of filoviruses as uniquely virulent agents to both human and wildlife communities but also implies a very complex transmission scenario that must be understood if we are to prevent or mitigate filovirus outbreaks in the future. Efforts of a global network of scientists and healthcare workers have expanded our knowledge of filoviruses to meet the growing threat of Ebola and Marburg hemorrhagic fevers in Africa. In recent decades, several newly emerging diseases have resulted in major threats to both affected communities and global public health. Viruses from wildlife hosts in particular, have exhibited a capability for cross-species transmission (CST), and have caused high-impact diseases in humans Such as Ebola and Marburg hemorrhagic fevers, Nipah and severe acute respiratory syndrome (SAILS). It has been estimated that about 60.3% (Jones et al. 2008) of human infectious diseases are of animal origin (zoonoses) and even some important viral diseases that are traditionally considered of human origin, for example measles and smallpox, may very well have their prehistoric origins in wildlife (Wolfe et al 2007). It maybe logical and prudent therefore, to anticipate that there are other, new filoviruses out there that will cross into humans at some point in time. If we anticipate that these will happen and wish to be prepared for and mitigate this potential, then an understanding of filoviruses as a biologic system in the environment will be essential to that process. We will need to know how the ecological dynamic of CST interacts with a 'new' viruse's evolutionary factors to overcome environmental, demographic and host-specific barriers to transmission and infectivity to humans.

Pinzon, Jorge E.↗

Emerging and Reemeriging Human Bunyavirus Infections and Climate Change

The Bunyaviridae family includes a growing number of viruses that have contributed to the burden of emerging and reemerging infectious diseases around the globe. Many of these viruses cause severe clinical outcomes in human and animal populations, the results of which can be detrimental to public health and the economies of affected communities. The threat to endemic and non-native regions is particularly high, and national and international public health agencies are often on alert. Many of the bunyaviruses cause severe clinical disease including hemorrhage, organ failure, and death leading to their high-risk classification. Hantaviruses and Rift Valley fever virus (RVFV) (genus Phlebovirus) are National Institute of Allergy and Infectious Diseases Category A priority pathogens in the United States. Viral hemorrhagic fevers, a classification that includes many bunyaviruses, are immediately notifiable in the European Union. The emergence of new and reemerging bunyaviruses has resulted in numerous human and animal fatalities. Outbreaks of Rift Valley fever (RVF) in East Africa (1997/1998, 2006/2007), Sudan (2007), Southern Africa (2008-2010), Kenya (1997/1998, 2006/2007) (Anyamba et al., 2009, 2010; Breiman et al., 2010; Grobbelaar et al., 2011; Woods et al., 2002) and Saudi Arabia & Yemen (2000, 2010) (Food and Agriculture Organization, 2000; Hjelle and Glass, 2000; Madani et al., 2003) and the emergence of Sin Nombre virus (1993) (Hjelle and Glass, 2000) and most recently Schmallenberg virus (2011) (DEFRA, 2012) are prime examples of the devastating and worldwide toll bunyaviruses have on health and economies. Climate variability (precipitation and temperature in particular) greatly influence the ecological conditions that drive arboviral disease outbreaks across the globe. Several human and animal disease outbreaks have been influenced by changes in climate associated with the El Niño Southern Oscillation (ENSO) phenomenon including the bunyaviruses RVFV and Sin Nombre (an etiologic agent of hantavirus pulmonary syndrome (HPS)), as well as Murray Valley encephalitis, chikungunya, and malaria to name but a few (Anyamba et al., 2009; Bouma and Dye, 1997; Chretien et al., 2007; Engelthaler et al., 1999; Kovats et al., 2003; Linthicum et al., 1999; Nicholls, 1986). Most bunyaviruses exhibit episodic outbreak patterns with seasonal or annual trends dependent upon climate conditions, vector abundance, and the proximity of a susceptible population. The implications for continued climate change are dire, especially with regard to vector-borne diseases, many of which can cause severe morbidity, sequelae, and death. Increased rainfall and widening endemicity as a result of climate change, compounded by the emergence of new viruses, poses a serious threat to a greater geographic range beyond the regions of endemicity.

Bunyavirus↗

Comparison of Multispectral Imaging and Traditional Fundoscopy in the Detection of Terrestrial Retinal and Optic Nerve Pathologies like those Encountered During and/or Immediately Following Long-Duration Spaceflight

INTRODUCTION: The purpose of this investigation was to evaluate if MultiColor Imaging (MCI) can replace color fundus photography (CFP) as a diagnostic screening tool during spaceflight. MCI significantly reduces crew time (approx. 115 minutes/session, 36 hours/year) by eliminating nominal on-orbit fundoscopy sessions, while also providing the option to capture a larger field of view (55 vs. 35). METHODS: A comprehensive PubMed literature search was conducted using the following key words: multicolor, multispectral, imaging, retina, choroid, optic nerve, optic disc, and papilledema. Publications were filtered based on optic nerve and chorioretinal pathologies matching those seen during or immediately after spaceflight: optic disc edema (ODE), cotton wool spots (CWS), retinal hemorrhage, pigment epithelial detachment (PED), and serous chorioretinopathy (SCR). In a separate effort, 44 multicolor images (30 abnormal) of terrestrial patients were graded and compared to corresponding color fundus images acquired at the Doheny Eye Centers and UCLA. RESULTS: The search identified 340 articles; 9 describing MCI in relevant pathologies, 6 comparing MCI to CFP. MCI is superior in detecting CWS (1 paper), PED (2 papers), retinal hemorrhages (2 papers), and choroidal folds (1 paper), and can better delineate extent or boundaries of subretinal fluid and identify areas of RPE damage in SCR (2 papers). On MCI, ODE was described as a hyperreflective ring with a green shift and indistinct disc margins, with equaldetectability as using CFP (3 papers). Grading at Doheny Eye Institute confirmed these findings. DISCUSSION: MCI can effectively detect all retinal and optic nerve findings detectable by CFP during and immediately post-spaceflight and represents a suitable replacement as an on-orbit diagnostic screening tool. Additionally, by eliminating the nominal on-orbit fundoscopy sessions, dozens of crew hours are spared per year by utilizing MCI.

Jorge Nagel↗

Development of a novel minigenome and recombinant VSV expressing Seoul hantavirus glycoprotein-based assays to identify anti-hantavirus therapeutics

Seoul virus (SEOV) is an emerging global health threat that can cause hemorrhagic fever with renal syndrome (HFRS), which results in case fatality rates of ~2%. There are no approved treatments for SEOV infections. We developed a cell-based assay system to identify potential antiviral compounds for SEOV and generated additional assays to characterize the mode of action of any promising antivirals. Here, to test if candidate antivirals targeted SEOV glycoprotein-mediated entry, we developed a recombinant reporter vesicular stomatitis virus expressing SEOV glycoproteins. To facilitate the identification of candidate antiviral compounds targeting viral transcription/replication, we successfully generated the first reported minigenome system for SEOV. This SEOV minigenome (SEOV-MG) screening assay will also serve as a prototype assay for discovery of small molecules inhibiting replication of other hantaviruses, including Andes and Sin Nombre viruses. Ours is a proof-of-concept study in which we tested several compounds previously reported to have activity against other negative-strand RNA viruses using our newly developed hantavirus antiviral screening systems. These systems can be used under lower biocontainment conditions than those needed for infectious viruses, and identified several compounds with robust anti-SEOV activity. Our findings have important implications for the development of anti-hantavirus therapeutics.

60 APPLIED LIFE SCIENCES↗

Superiority of compensatory reserve measurement compared with the Shock index for early and accurate detection of reduced central blood volume status

Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock. We measured HR, SBP, and CRM in 172 human subjects (19–55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI. The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater (p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94–0.97) compared with 0.91 (0.89–0.94) for SI (p = 0.0002). Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia.

60 APPLIED LIFE SCIENCES↗

Lassa virus protein–protein interactions as mediators of Lassa fever pathogenesis

Viral hemorrhagic Lassa fever (LF), caused by Lassa virus (LASV), is a significant public health concern endemic in West Africa with high morbidity and mortality rates, limited treatment options, and potential for international spread. Despite advances in interrogating its epidemiology and clinical manifestations, the molecular mechanisms driving pathogenesis of LASV and other arenaviruses remain incompletely understood. This review synthesizes current knowledge regarding the role of LASV host-virus interactions in mediating the pathogenesis of LF, with emphasis on interactions between viral and host proteins. Through investigation of these critical protein–protein interactions, we identify potential therapeutic targets and discuss their implications for development of medical countermeasures including antiviral drugs. This review provides an update in recent literature of significant LASV host-virus interactions important in informing the development of targeted therapies and improving clinical outcomes for LF patients. Knowledge gaps are highlighted as opportunities for future research efforts that would advance the field of LASV and arenavirus pathogenesis.

60 APPLIED LIFE SCIENCES↗

An extended focused assessment with sonography in trauma ultrasound tissue-mimicking phantom for developing automated diagnostic technologies

Medical imaging-based triage is critical for ensuring medical treatment is timely and prioritized. However, without proper image collection and interpretation, triage decisions can be hard to make. While automation approaches can enhance these triage applications, tissue phantoms must be developed to train and mature these novel technologies. Here, we have developed a tissue phantom modeling the ultrasound views imaged during the enhanced focused assessment with sonography in trauma exam (eFAST). The tissue phantom utilized synthetic clear ballistic gel with carveouts in the abdomen and rib cage corresponding to the various eFAST scan points. Various approaches were taken to simulate proper physiology without injuries present or to mimic pneumothorax, hemothorax, or abdominal hemorrhage at multiple locations in the torso. Multiple ultrasound imaging systems were used to acquire ultrasound scans with or without injury present and were used to train deep learning image classification predictive models. Performance of the artificial intelligent (AI) models trained in this study achieved over 97% accuracy for each eFAST scan site. We used a previously trained AI model for pneumothorax which achieved 74% accuracy in blind predictions for images collected with the novel eFAST tissue phantom. Grad-CAM heat map overlays for the predictions identified that the AI models were tracking the area of interest for each scan point in the tissue phantom. Overall, the eFAST tissue phantom ultrasound scans resembled human images and were successful in training AI models. Tissue phantoms are critical first steps in troubleshooting and developing medical imaging automation technologies for this application that can accelerate the widespread use of ultrasound imaging for emergency triage.

60 APPLIED LIFE SCIENCES↗

Deep learning models for interpretation of point of care ultrasound in military working dogs

Introduction: Military working dogs (MWDs) are essential for military operations in a wide range of missions. With this pivotal role, MWDs can become casualties requiring specialized veterinary care that may not always be available far forward on the battlefield. Some injuries such as pneumothorax, hemothorax, or abdominal hemorrhage can be diagnosed using point of care ultrasound (POCUS) such as the Global FAST® exam. This presents a unique opportunity for artificial intelligence (AI) to aid in the interpretation of ultrasound images. In this article, deep learning classification neural networks were developed for POCUS assessment in MWDs. Methods: Images were collected in five MWDs under general anesthesia or deep sedation for all scan points in the Global FAST® exam. For representative injuries, a cadaver model was used from which positive and negative injury images were captured. A total of 327 ultrasound clips were captured and split across scan points for training three different AI network architectures: MobileNetV2, DarkNet-19, and ShrapML. Gradient class activation mapping (GradCAM) overlays were generated for representative images to better explain AI predictions. Results: Performance of AI models reached over 82% accuracy for all scan points. The model with the highest performance was trained with the MobileNetV2 network for the cystocolic scan point achieving 99.8% accuracy. Across all trained networks the diaphragmatic hepatorenal scan point had the best overall performance. However, GradCAM overlays showed that the models with highest accuracy, like MobileNetV2, were not always identifying relevant features. Conversely, the GradCAM heatmaps for ShrapML show general agreement with regions most indicative of fluid accumulation. Discussion: Overall, the AI models developed can automate POCUS predictions in MWDs. Preliminarily, ShrapML had the strongest performance and prediction rate paired with accurately tracking fluid accumulation sites, making it the most suitable option for eventual real-time deployment with ultrasound systems. Further integration of this technology with imaging technologies will expand use of POCUS-based triage of MWDs.

59 BASIC BIOLOGICAL SCIENCES↗

Nanoengineered Shape-Memory Hemostat

Uncontrolled hemorrhage is the predominant cause of preventable combat deaths. Various biomaterials serve as hemostatic agents due to their procoagulant or absorptive activity. However, these biomaterials often lack expansion capabilities, which severely limits use in noncompressible wounds. This study combines a hemostatic nanocomposite with a shape-memory polymer foam to design a composite material with both hemostatic and physical expansion properties. This composite is fabricated in two formulations: a foam externally coated in a highly concentrated nanocomposite (“coated composite”) and a foam containing a diluted nanocomposite infused throughout its pores (“infused composite”). Both formulations retain the shape-memory foam's expansion property. Further, the coated composite shows improved fluid uptake (>2-fold) versus infused composites or foam. The nanocomposite component dissociates from the foam under degradative conditions, with the foam remaining stable for 30 days. Hemostatic studies illustrate that the coated composite reduces the clotting time by ≈20%. Alternatively, the infused composite improves clotting over a larger distance (up to ≈2× distance from the composite). These results signify a modular hemostatic ability: the coated composite reduces clotting and improves fluid uptake, while the infused composite achieves diffuse clotting and maintains mechanical properties. Thus, these materials pose a strong potential for use in noncompressible wounds.

60 APPLIED LIFE SCIENCES↗

Delineating the mechanism of anti-Lassa virus GPC-A neutralizing antibodies

Lassa virus (LASV) is the etiologic agent of Lassa Fever, a hemorrhagic disease that is endemic to West Africa. During LASV infection, LASV glycoprotein (GP) engages with multiple host receptors for cell entry. Neutralizing antibodies against GP are rare and principally target quaternary epitopes displayed only on the metastable, pre-fusion conformation of GP. Currently, the structural features of the neutralizing GPC-A antibody competition group are understudied. Structures of two GPC-A antibodies presented here demonstrate that they bind the side of the pre-fusion GP trimer, bridging the GP1 and GP2 subunits. Complementary biochemical analyses indicate that antibody 25.10C, which is broadly specific, neutralizes by inhibiting binding of the endosomal receptor LAMP1 and also by blocking membrane fusion. The other GPC-A antibody, 36.1F, which is lineage-specific, prevents LAMP1 association only. These data illuminate a site of vulnerability on LASV GP and will guide efforts to elicit broadly reactive therapeutics and vaccines.

59 BASIC BIOLOGICAL SCIENCES↗