Project description:Astronauts on a mission to Mars would be exposed for up to 3 years to galactic cosmic rays (GCR)--made up of high-energy protons and high charge (Z) and energy (E) (HZE) nuclei. GCR exposure rate increases about three times as spacecraft venture out of Earth orbit into deep space where protection of the Earth's magnetosphere and solid body are lost. NASA's radiation standard limits astronaut exposures to a 3% risk of exposure induced death (REID) at the upper 95% confidence interval (CI) of the risk estimate. Fatal cancer risk has been considered the dominant risk for GCR, however recent epidemiological analysis of radiation risks for circulatory diseases allow for predictions of REID for circulatory diseases to be included with cancer risk predictions for space missions. Using NASA's models of risks and uncertainties, we predicted that central estimates for radiation induced mortality and morbidity could exceed 5% and 10% with upper 95% CI near 10% and 20%, respectively for a Mars mission. Additional risks to the central nervous system (CNS) and qualitative differences in the biological effects of GCR compared to terrestrial radiation may significantly increase these estimates, and will require new knowledge to evaluate.
Project description:C57BL/6 mice were immunized with Coxiella burnetii vaccine Q-VAX (Seqirus) and monitored for up to 83 days post immunization. Two different routes of immunization were observed - subcutaneous and intramuscular. Subcutaneously immunized animals were boosted on day 67.
Project description:Aerosol emissions from wind instruments are a suspected route of transmission for airborne infectious diseases, such as SARS-CoV-2. We evaluated aerosol number emissions (from 0.25 to 35.15 μm) from 81 volunteer performers of both sexes and varied age (12 to 63 years) while playing wind instruments (bassoon, clarinet, flute, French horn, oboe, piccolo, saxophone, trombone, trumpet, and tuba) or singing. Measured emissions spanned more than two orders of magnitude, ranging in rate from < 8 to 1,815 particles s-1, with brass instruments, on average, producing 191% (95% CI 81-367%) more aerosol than woodwinds. Being male was associated with a 70% increase in emissions (vs. female; 95% CI 9-166%). Each 1 dBA increase in sound pressure level was associated with a 28% increase (95% CI 10-40%) in emissions from brass instruments; sound pressure level was not associated with woodwind emissions. Age was not a significant predictor of emissions. The use of bell covers reduced aerosol emissions from three brass instruments tested (trombone, tuba, and trumpet), with average reductions ranging from 53 to 73%, but not for the two woodwind instruments tested (oboe and clarinet). Results from this work can facilitate infectious disease risk management for the performing arts.
Project description:Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-Å cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may result in cross-linking of neighboring spikes to prevent conformational requirements for viral fusion. Prophylaxis or postexposure therapy with these mAbs protected mice against lethal aerosol challenge with VEEV. Our study defines functional and structural mechanisms of mAb protection and suggests that multiple antigenic determinants on VEEV can be targeted for vaccine or antibody-based therapeutic development.
Project description:BackgroundThe aerosol box was rapidly developed and disseminated to minimize viral exposure during aerosolizing procedures during the COVID-19 pandemic, yet users may not understand how to use and clean the device. This could potentially lead to increased viral exposure to subsequent patients and practitioners. We evaluated intraoperative contamination and aerosol box decontamination and the impact of a preoperative educational visual aid.MethodsUsing a double-blinded randomized design, forty-four anesthesiology trainees and faculty completed a simulated anesthetic case using an aerosol box contaminated with a fluorescent marker; half of the subjects received a visual aid prior to the simulation. Intraoperative contamination was evaluated at 10 standardized locations using an ultraviolet (UV) light. Next, subjects were instructed to clean the aerosol box for use on the next patient. Following cleaning, the box was evaluated for decontamination using an UV light.ResultsMedian total contamination score was significantly reduced in the experimental group (5.0 vs. 10.0, P < 0.001). The aerosol box was completely cleaned by 36.4% of subjects in the experimental group compared to 4.5% in the control group (P = 0.009).ConclusionsThe use of a visual aid significantly decreased intraoperative contamination and improved box cleaning. Despite these findings, a potentially clinically significant amount of viral exposure may exist. Thorough evaluation of the risks and benefits of the aerosol box should be completed prior to use. If an aerosol box is used, a visual aid should be considered to remind practitioners how to best use and clean the box.
Project description:Fine particulate matter (PM2.5) is known to have an adverse impact on public health and is an important climate forcer. Secondary organic aerosol (SOA) contributes up to 80% of PM2.5 worldwide and multiphase reactions are an important pathway to form SOA. Aerosol-phase state is thought to influence the reactive uptake of gas-phase precursors to aerosol particles by altering diffusion rates within particles. Current air quality models do not include the impact of diffusion-limiting organic coatings on SOA formation. This work examines how α-pinene-derived organic coatings change the predicted formation of SOA from the acid-catalyzed multiphase reactions of isoprene epoxydiols (IEPOX). A box model, with inputs provided from field measurements taken at the Look Rock (LRK) site in Great Smokey Mountains National Park during the 2013 Southern Oxidant and Aerosol Study (SOAS), was modified to incorporate the latest laboratory-based kinetic data accounting for organic coating influences. Including an organic coating influence reduced the modeled reactive uptake when relative humidity was in the 55-80% range, with predicted IEPOX-derived SOA being reduced by up to 33%. Only sensitivity cases with a large increase in Henry's Law values of an order of magnitude or more or in particle reaction rates resulted in the large statistically significant differences form base model performance. These results suggest an organic coating layer could have an impact on IEPOX-derived SOA formation and warrant consideration in regional and global scale models.
Project description:Each year, approximately five million people die worldwide from putatively vaccine-preventable mucosally transmitted diseases. With respect to mass vaccination campaigns, one strategy to cope with this formidable challenge is aerosol vaccine delivery, which offers potential safety, logistical, and cost-saving advantages over traditional vaccination routes. Additionally, aerosol vaccination may elicit pivotal mucosal immune responses that could contain or eliminate mucosally transmitted pathogens in a preventative or therapeutic vaccine context. In this current preclinical non-human primate investigation, we demonstrate the feasibility of aerosol vaccination with the recombinant poxvirus-based vaccine vectors NYVAC and MVA. Real-time in vivo scintigraphy experiments with radiolabeled, aerosol-administered NYVAC-C (Clade C, HIV-1 vaccine) and MVA-HPV vaccines revealed consistent mucosal delivery to the respiratory tract. Furthermore, aerosol delivery of the vaccines was safe, inducing no vaccine-associated pathology, in particular in the brain and lungs, and was immunogenic. Administration of a DNA-C/NYVAC-C prime/boost regime resulted in both systemic and anal-genital HIV-specific immune responses that were still detectable 5 months after immunization. Thus, aerosol vaccination with NYVAC and MVA vectored vaccines constitutes a tool for large-scale vaccine efforts against mucosally transmitted pathogens.
Project description:Vaccines are among the most cost-effective public health measures for controlling infectious diseases. Coxiella burnetii is the etiological agent of Q fever, a disease with a wide clinical spectrum that ranges from mild symptoms, such as fever and fatigue, to more severe disease, such as pneumonia and endocarditis. The formalin-inactivated whole-cell vaccine Q-VAX® contains hundreds of antigens and confers lifelong protection in humans, but prior sensitization from infection or vaccination can result in deleterious reactogenic responses to vaccination. Consequently, there is great interest in developing non-reactogenic alternatives based on adjuvanted recombinant proteins. In this study, we aimed to develop a multivalent vaccine that conferred protection with reduced reactogenicity. We hypothesized that a multivalent vaccine consisting of multiple antigens would be more immunogenic and protective than a monovalent vaccine owing to the large number of potential protective antigens in the C. burnetii proteome. To address this, we identified immunogenic T and B cell antigens, and selected proteins were purified to evaluate with a combination adjuvant (IVAX-1), with or without C. burnetii lipopolysaccharide (LPS) in immunogenicity studies in vivo in mice and in a Hartley guinea pig intratracheal aerosol challenge model using C. burnetii strain NMI RSA 493. The data showed that multivalent vaccines are more immunogenic than monovalent vaccines and more closely emulate the protection achieved by Q-VAX. Although six antigens were the most immunogenic, we also discovered that multiplexing beyond four antigens introduces detectable reactogenicity, indicating that there is an upper limit to the number of antigens that can be safely included in a multivalent Q-fever vaccine. C. burnetii LPS also demonstrates efficacy as a vaccine antigen in conferring protection in an otherwise monovalent vaccine formulation, suggesting that its addition in multivalent vaccines, as demonstrated by a quadrivalent formulation, would improve protective responses.
Project description:RationaleRecently, commercial indoor trampoline parks have been opened around the globe, and both the number of venues and the park users are increasing. Academic literatures have largely focused on home trampoline related injuries, and less is known about the injuries associated with trampoline parks due to the limited number of studies or cases reported. In this report, we present a complete spinal cord injury sustained at a commercial indoor trampoline park.Patient concernsA 26-year old male developed tetraplegia after plainly jumping on the trampolines and diving into one of the foam pits head first.DiagnosisC-spine CT revealed bilateral interfacetal dislocation on C6-7, and his C-spine MRI showed anterior translational injury at C6-7 with severe cord encroachment and complete discoligamentous complex disruption. He was diagnosed with complete spinal cord injury.InterventionsThe patient underwent 30 minutes each of physical therapy and occupational therapy twice a day for a total of 25 days of in-patient rehabilitation. Interventions included tilt table, passive range of motion exercises, functional electrical stimulation, sitting balance training, upper extremity strengthening exercise, and hand manipulation exercises.OutcomeDespite intensive rehabilitation and the patient's good spirit, there was no functional change in all physical examinations between evaluations at initial and at discharge.LessonsIn conclusion, we aim to alert the risks associated with improper use of trampolines, promote safer entertainment environment, and aid in developing mandatory safety measures. We hope to alert the risks associated with improper use of trampolines, promote safer entertainment environment, and aid in developing mandatory safety measures.