Human Surrogates Research Articles

Kinematic and Injury Response of Reclined PMHS in Frontal Impacts.

Frontal impacts with reclined occupants are rare but severe, and they are anticipated to become more common with the introduction of vehicles with automated driving capabilities. Computational and physical human surrogates are needed to design and evaluate injury countermeasures for reclined occupants, but the validity of such surrogates in a reclined posture is unknown. Experiments with post-mortem human subjects (PMHS) in a recline posture are needed both to define biofidelity targets for other surrogates and to describe the biomechanical response of reclined occupants in restrained frontal impacts. The goal of this study was to evaluate the kinematic and injury response of reclined PMHS in 30 g, 50 km/h frontal sled tests. Five midsize adult male PMHS were tested. A simplified semi-rigid seat with an anti-submarining pan and a non-production threepoint seatbelt (pre-tensioned, force-limited, seat-integrated) were used. Global motions and local accelerations of the head, pelvis, and multiple vertebrae were measured. Seat and seatbelt forces were also measured. Injuries were assessed via post-test dissection. The initial reclined posture aligned body regions (pelvis, lumbar spine, and ribcage) in a way that reduced the likelihood of effective restraint by the seat and seatbelt: the occupant's pelvis was initially rotated posteriorly, priming the occupant for submarining, and the lumbar spine was loaded in combined compression and bending due to the inertia of the upper torso during forward excursion. Coupled with the high restraining forces of the seat and seatbelt, the unfavorable kinematics resulted in injuries of the sacrum/coccyx (four of five PMHS injured), iliac wing (two of five PMHS injured), lumbar spine (three of five PMHS injured), and ribcage (all five PMHS suffered sternal fractures, and three of five PMHS suffered seven or more rib fractures). The kinematic and injury outcomes strongly motivate the development of injury criteria for the lumbar spine and pelvis, the inclusion of intrinsic variability (e.g., abdomen depth and pelvis shape) in computational simulations of frontal impacts with reclined occupants, and the adaptation of comprehensive restraint paradigms to predicted variability of occupant posture.

Modelling of micro-particles perforations into human tissue surrogate: Numerical and analytical aspects

Investigating high-speed microparticle impact responses into soft tissue is essential to several fields like medicine and transdermal delivery of pharmaceuticals. Various simulants such as ballistic gelatin, rubber, and polymers have been developed to replace the biological body in experimental investigation, considering the practical and ethical issues. The synthetic polymer SEBS gel (styrene-ethylene-butylene-styrene) interests some scientists in recent years because it involves several benefits like environmental stability, reproducibility, mechanical consistency, transparency, and biofidelic ability to reproduce human soft tissue behavior. A few experiments have been performed on the penetration of SEBS gel. But its physical behavior under high-velocity impact, especially in micro-scale, is yet to be investigated. As the earliest meshless method, Smoothed Particles Hydrodynamics (SPH) has been identified to have a great potential in simulating extremely large deformation. This study employs a numerical model by the SPH method to investigate the response of the SEBS gel under micro-penetration, combined with an elastic-hydrodynamic constitutive law. The range of Young’s modulus is firstly described for the SEBS gel under micro-impacts, which is validated against experimental data. Supplementally, the suitability of three types of analytical models depending on fitting coefficients is also discussed for micro penetrations into soft tissue.

A Comparison of Porphyrin Photosensitizers in Photodynamic Inactivation of RNA and DNA Bacteriophages.

Effective broad-spectrum antiviral treatments are in dire need as disinfectants and therapeutic alternatives. One such method of disinfection is photodynamic inactivation, which involves the production of reactive oxygen species from dissolved oxygen in response to light-stimulated photosensitizers. This study evaluated the efficacy of functionalized porphyrin compounds for photodynamic inactivation of bacteriophages as human virus surrogates. A blue-light light emitting diode (LED) lamp was used to activate porphyrin compounds in aqueous solution (phosphate buffer). The DNA bacteriophages ΦX174 and P22 were more resistant to porphyrin TMPyP photodynamic inactivation than RNA bacteriophage fr, with increasing rates of inactivation in the order: ΦX174 << P22 << fr. Bacteriophage ΦX174 was therefore considered a resistant virus suitable for the evaluation of three additional porphyrins. These porphyrins were synthesized from TMPyP by inclusion of a central palladium ion (PdT4) and/or the addition of a hydrophobic C14 chain (PdC14 or C14). While the inactivation rate of bacteriophage ΦX174 via TMPyP was similar to previous reports of resistant viruses, ΦX174 inactivation increased by a factor of approximately 2.5 using the metalloporphyrins PdT4 and PdC14. The order of porphyrin effectiveness was TMPyP < C14 < PdT4 < PdC14, indicating that both Pd2+ ligation and C14 functionalization aided virus inactivation.

Optimization of Underbody Blast Energy-Attenuating Seat Mechanisms Using Modified MADYMO Human Body Models.

Though energy attenuating (EA) seats for air and spacecraft applications have existed for decades, they have not yet been fully characterized for their energy attenuation capability or resulting effect on occupant protection in vertical underbody blast. EA seats utilize stroking mechanisms to absorb energy and reduce the vertical forces imparted on the occupant's pelvis and lower spine. Using dynamic rigid-body modeling, a virtual tool to determine optimal force and deflection limits was developed to reduce pelvis and lower spine injuries in underbody blast events using a generic seat model. The tool consists of a mathematical dynamic model (MADYMO)-modified human body model (HBM), basic EA seat model, and an optimizing sequence using modefrontier software. This optimizing tool may be shared with EA seat manufacturers and applied to military seat development efforts for EA mechanisms for a given occupant and designated blast severity. To optimally tune the EA seat response, the MADYMO human body model was first updated to improve its fidelity in kinematic response data for high rate vertical accelerative loading relative to experimental data from laboratory simulated underbody blast tests using postmortem human surrogates (PMHS). Subsequently, using available injury criteria for underbody blast, the optimization tool demonstrated the ability to identify successful EA mechanism critical design value configurations to reduce forces and accelerations in the pelvis and lower spine HBM to presumed noninjurious levels. This tool could be tailored by varying input pulses, force and deflection limits, and occupant size to evaluate EA mechanism designs.

Rapid and Repetitive Inactivation of SARS-CoV-2 and Human Coronavirus on Self-Disinfecting Anionic Polymers.

While the ongoing COVID‐19 pandemic affirms an urgent global need for effective vaccines as second and third infection waves are spreading worldwide and generating new mutant virus strains, it has also revealed the importance of mitigating the transmission of SARS‐CoV‐2 through the introduction of restrictive social practices. Here, it is demonstrated that an architecturally‐ and chemically‐diverse family of nanostructured anionic polymers yield a rapid and continuous disinfecting alternative to inactivate coronaviruses and prevent their transmission from contact with contaminated surfaces. Operating on a dramatic pH‐drop mechanism along the polymer/pathogen interface, polymers of this archetype inactivate the SARS‐CoV‐2 virus, as well as a human coronavirus surrogate (HCoV‐229E), to the minimum detection limit within minutes. Application of these anionic polymers to frequently touched surfaces in medical, educational, and public‐transportation facilities, or personal protection equipment, can provide rapid and repetitive protection without detrimental health or environmental complications.

Effect of Plant-Derived Proteases on Infectivity of Tulane Virus, Murine Norovirus, and Hepatitis A Virus

Plant-derived proteases, bromelain, papain, and ficin, are broad-acting enzymes with generally recognized as safe status for foods and have current application in several food industries. These proteases have also been reported to have antimicrobial properties. This study investigated the efficacy of commercially prepared bromelain, papain, and ficin, individually and combined (2,500 ppm of crude extract), for inactivation of hepatitis A virus (HAV) and human norovirus surrogates, Tulane virus (TV), and murine norovirus (MNV). Various treatment temperatures (45, 50, or 55°C), times (10 or 60 min), and pH values (5.5 or 7.0) in the presence of cysteine (2 mM) were evaluated. Inactivation was assessed by infectivity in plaque assay for TV and MNV and by median tissue culture infective dose for HAV. No reduction in infectious TV or HAV was attributed to the plant-derived proteases at any of the conditions tested. Infectious MNV was reduced by 1 to 3 log PFU/mL; the most effective treatment was bromelain at pH 7 and 50°C for 10 min. A time course study with MNV in bromelain at 50°C indicated that a 2-log PFU/mL reduction could be achieved within 6 min, but extended treatment of 15 min was still insufficient to eliminate infectious MNV. The lack of or limited efficacy of bromelain, papain, and ficin on HAV, TV, and MNV, even at elevated temperatures and exposure times, suggests the plant-derived proteases are not commercially applicable for inactivation of virus on commodities or materials that could not also withstand mild heat treatment. The variable susceptibilities observed between TV and MNV illustrate limitations in utilization of surrogates for predicting pathogen behavior for a structure-specific treatment.

Embryo implantation in the laboratory: an update on current techniques.

The embryo implantation process is crucial for the correct establishment and progress of pregnancy. During implantation, the blastocyst trophectoderm cells attach to the epithelium of the endometrium, triggering intense cell-to-cell crosstalk that leads to trophoblast outgrowth, invasion of the endometrial tissue, and formation of the placenta. However, this process, which is vital for embryo and foetal development in utero, is still elusive to experimentation because of its inaccessibility. Experimental implantation is cumbersome and impractical in adult animal models and is inconceivable in humans. A number of custom experimental solutions have been proposed to recreate different stages of the implantation process in vitro, by combining a human embryo (or a human embryo surrogate) and endometrial cells (or a surrogate for the endometrial tissue). In vitro models allow rapid high-throughput interrogation of embryos and cells, and efficient screening of molecules, such as cytokines, drugs, or transcription factors, that control embryo implantation and the receptivity of the endometrium. However, the broad selection of available in vitro systems makes it complicated to decide which system best fits the needs of a specific experiment or scientific question. To orient the reader, this review will explore the experimental options proposed in the literature, and classify them into amenable categories based on the embryo/cell pairs employed.The goal is to give an overview of the tools available to study the complex process of human embryo implantation, and explain the differences between them, including the advantages and disadvantages of each system. We performed a comprehensive review of the literature to come up with different categories that mimic the different stages of embryo implantation in vitro, ranging from initial blastocyst apposition to later stages of trophoblast invasion or gastrulation. We will also review recent breakthrough advances on stem cells and organoids, assembling embryo-like structures and endometrial tissues. We highlight the most relevant systems and describe the most significant experiments. We focus on in vitro systems that have contributed to the study of human reproduction by discovering molecules that control implantation, including hormones, signalling molecules, transcription factors and cytokines. The momentum of this field is growing thanks to the use of stem cells to build embryo-like structures and endometrial tissues, and the use of bioengineering to extend the life of embryos in culture. We propose to merge bioengineering methods derived from the fields of stem cells and reproduction to develop new systems covering a wider window of the implantation process.

Evaluation of behaviour of an obese human body model in frontal sled tests

The goal of this study was to assess the behaviour of an obese Human Body Model (HBM) in frontal sled tests. The results of rear-seat sled tests with an obese (BMI = 35) Post Mortem Human Surrogate (PMHS) were used to evaluate the performance of the obese HBM in matching conditions. Also, the responses of a non-obese HBM (BMI = 25) and the obese HBM were compared in a front-seat frontal impact test. In the rear-seat tests, both the obese HBM and the obese PMHS experienced a large forward excursion, delayed lap belt engagement with the pelvis, and a reclined-to-upright torso angle throughout the tests, which were the effects of large body mass and thick flesh. In the front-seat simulations, the obese HBM experienced a larger excursion than the non-obese HBM. The obese HBM can be a useful tool to design and optimise restraint system for front-seat occupants with obesity.

A detailed finite element model of a mid-sized male for the investigation of traffic pedestrian accidents.

The pedestrian is one of the most vulnerable road users and comprises approximately 23% of the road crash-related fatalities in the world. To protect pedestrians during Car-to-Pedestrian Collisions (CPC), subsystem impact tests are used in regulations. These tests provide insight but cannot characterize the complex vehicle-pedestrian interaction. The main purpose of this study was to develop and validate a detailed pedestrian Finite Element (FE) model corresponding to a 50th percentile male to predict CPC induced injuries. The model geometry was reconstructed using a multi-modality protocol from medical images and exterior scan data corresponding to a mid-sized male volunteer. To investigate injury response, this model included internal organs, muscles and vessels. The lower extremity, shoulder and upper body of the model were validated against Post Mortem Human Surrogate (PMHS) test data in valgus bending, and lateral/anterior-lateral blunt impacts, respectively. The whole-body pedestrian model was validated in CPC simulations using a mid-sized sedan and simplified generic vehicles bucks and previously unpublished PMHS coronal knee angle data. In the component validations, the responses of the FE model were mostly within PMHS test corridors and in whole body validations the kinematic and injury responses predicted by the model showed similar trends to PMHS test data. Overall, the detailed model showed higher biofidelity, especially in the upper body regions, compared to a previously reported simplified pedestrian model, which recommends using it in future pedestrian automotive safety research.

Laboratory Assessment of a Headband-Mounted Sensor for Measurement of Head Impact Rotational Kinematics.

Head impact sensors measure head kinematics in sports, and sensor accuracy is crucial for investigating the potential link between repetitive head loading and clinical outcomes. Many validation studies mount sensors to human head surrogates and compare kinematic measures during loading from a linear impactor. These studies are often unable to distinguish intrinsic instrumentation limitations from variability caused by sensor coupling. The aim of the current study was to evaluate intrinsic sensor error in angular velocity in the absence of coupling error for a common head impact sensor. Two Triax SIM-G sensors were rigidly attached to a preclinical rotational injury device and subjected to rotational events to assess sensor reproducibility and accuracy. Peak angular velocities between the SIM-G sensors paired for each test were correlated (R2 > 0.99, y = 1.00x, p < 0.001). SIM-G peak angular velocity correlated with the reference (R2 = 0.96, y = 0.82x, p < 0.001); however, SIM-G underestimated the magnitude by 15.0% ± 1.7% (p < 0.001). SIM-G angular velocity rise time (5% to 100% of peak) correlated with the reference (R2 = 0.97, y = 1.06x, p < 0.001) but exhibited a slower fall time (100% to 5% of peak) by 9.0 ± 3.7 ms (p < 0.001). Assessing sensor performance when rigidly coupled is a crucial first step to interpret on-field SIM-G rotational kinematic data. Further testing in increasing biofidelic conditions is needed to fully characterize error from other sources, such as coupling.

Characterization of Negative Allosteric Modulators of the Calcium-Sensing Receptor for Repurposing as a Treatment of Asthma.

Asthma is still an incurable disease, and there is a recognized need for novel small-molecule therapies for people with asthma, especially those poorly controlled by current treatments. We previously demonstrated that calcium-sensing receptor (CaSR) negative allosteric modulators (NAMs), calcilytics, uniquely suppress both airway hyperresponsiveness (AHR) and inflammation in human cells and murine asthma surrogates. Here we assess the feasibility of repurposing four CaSR NAMs, which were originally developed for oral therapy for osteoporosis and previously tested in the clinic as a novel, single, and comprehensive topical antiasthma therapy. We address the hypotheses, using murine asthma surrogates, that topically delivered CaSR NAMs 1) abolish AHR; 2) are unlikely to cause unwanted systemic effects; 3) are suitable for topical application; and 4) inhibit airway inflammation to the same degree as the current standard of care, inhaled corticosteroids, and, furthermore, inhibit airway remodeling. All four CaSR NAMs inhibited poly-L-arginine-induced AHR in naïve mice and suppressed both AHR and airway inflammation in a murine surrogate of acute asthma, confirming class specificity. Repeated exposure to inhaled CaSR NAMs did not alter blood pressure, heart rate, or serum calcium concentrations. Optimal candidates for repurposing were identified based on anti-AHR/inflammatory activities, pharmacokinetics/pharmacodynamics, formulation, and micronization studies. Whereas both inhaled CaSR NAMs and inhaled corticosteroids reduced airways inflammation, only the former prevented goblet cell hyperplasia in a chronic asthma model. We conclude that inhaled CaSR NAMs are likely a single, safe, and effective topical therapy for human asthma, abolishing AHR, suppressing airways inflammation, and abrogating some features of airway remodeling. SIGNIFICANCE STATEMENT: Calcium-sensing receptor (CaSR) negative allosteric modulators (NAMs) reduce airway smooth muscle hyperresponsiveness, reverse airway inflammation as efficiently as topical corticosteroids, and suppress airway remodeling in asthma surrogates. CaSR NAMs, which were initially developed for oral therapy of osteoporosis proved inefficacious for this indication despite being safe and well tolerated. Here we show that structurally unrelated CaSR NAMs are suitable for inhaled delivery and represent a one-stop, steroid-free approach to asthma control and prophylaxis.

Microbiologic Proof-Of-Concept: A Novel Device Combining UV Light And Ozone For Human Skin Antisepsis

Abstract Introduction/Objective Hand hygiene (HH) decreases healthcare-associated infections (HAI). Available products include alcohol-based gels, foams, wipes, and “gold-standard” hand-washing with soap and water. We tested an investigational device (HyLuxO3; GMI, LLC, patent pending) for antimicrobial effect (AME). HyLuxO3 was engineered to deliver UV-C light energy and high velocity O3 airflow to safely achieve human skin antisepsis within OSHA and EPA regulatory limits. Combined UV and O3 has yet to be evaluated for HH and may demonstrate synergistic AME. Methods HyLuxO3 was tested on LB agar to titrate device variables to ascertain intensities for optimal AME; later testing was performed on VITRO-SKIN (Florida Suncare Testing, Bunnell, FL), a human skin surrogate. ATCC strains of MRSA, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were used to test AME vs. vegetative microbes; Bacillus atrophaeus spores were used as a surrogate for C. difficile. Tested variables included time under device, [O3], airflow velocity, 222 and/or 254 nm UV light, sample distance from UV lamp, and UV beam width. Positive controls were used to calculate log-kill curves for AME. Results Similar results were seen on LB agar and VITRO-SKIN. &amp;gt;7 log-kill and &amp;gt;5 log-kill were acheived vs. vegetative microbes (&amp;lt;30 sec) and spores (60 sec), respectively, under optimized variables. Presence of UV light and sample distance from and time under the device were the most important variables. 254 nm UV had a significantly better AME than 222 nm; combining both UV lamps had a significant synergistic AME. The narrowest UV beam (2 mm) yielded the greatest AME (total energy input kept constant). Adding O3 to UV had a modest but significant synergistic effect; optimal [O3] was 0.3-0.8 ppm. Changing airflow velocity had no significant effect on AME. Conclusion HyLuxO3 is a novel device that achieves &amp;gt;7 log-kill vs. common pathogenic vegetative microbes and &amp;gt;5 log-kill vs. spores using combined UV light and [O3] safe for human skin antisepsis (and surface/fomite decontamination)- and- yields such impressive AME on faster timescales than those required by bleach/other chemical products unsuitable for human skin. Future studies on human hands (using many other microbes) will determine if HyLuxO3 meets regulatory and efficacy requirements for use in and beyond healthcare settings, especially with the specter of emerging respiratory viruses.

Evaluation of the Whole Body Spine Response to Sub-Injurious Vertical Loading

It is critical to understand the relationship between under-body blast (UBB) loading and occupant response to provide optimal protection to the warfighter from serious injuries, many of which affect the spine. Previous studies have examined component and whole body response to accelerative based UBB loading. While these studies both informed injury prediction efforts and examined the shortcomings of traditional anthropomorphic test devices in the evaluation of human injury, few studies provide response data against which future models could be compared and evaluated. The current study examines four different loading conditions on a seated occupant that demonstrate the effects of changes in the floor, seat, personal protective equipment (PPE), and reclined posture on whole body post-mortem human surrogate (PMHS) spinal response in a sub-injurious loading range. Twelve PMHS were tested across floor velocities and time-to-peak (TTP) that ranged from 4.0 to 8.0 m/s and 2 to 5 ms, respectively. To focus on sub-injurious response, seat velocities were kept at 4.0 m/s and TTP ranged from 5 to 35 ms. Results demonstrated that spine response is sensitive to changes in TTP and the presence of PPE. However, spine response is largely insensitive to changes in floor loading. Data from these experiments have also served to develop response corridors that can be used to assess the performance and predictive capability of new test models used as human surrogates in high-rate vertical loading experiments.

Efficacy of novel aqueous photo-chlorine dioxide against a human norovirus surrogate, bacteriophage MS2 and Clostridium difficile endospores, in suspension, on stainless steel and under greenhouse conditions.

The efficacy of a novel photochemical method for generating chlorine dioxide (photoClO2 ) was evaluated against human noroviruses (HuNoV) surrogate, bacteriophage MS2, and Clostridium difficile endospores. Chlorine dioxide was generated by mixing 1% sodium chlorite with 10 parts-per-million (ppm) Eosin Y and irradiating with a photo-activator-excitable light. PhotoClO2 efficacy was assessed against bacteriophage MS2 and C. difficile endospores in suspension, on hard surfaces and greenhouse conditions under soiled and unsoiled conditions. The estimated effective photoClO2 produced and consumed was 20·39±0·16ppm at a rate of 8·16ppm per min in a 1% sodium chlorite solution. In suspension, MS2 phage was reduced by 3·35 and >5·10 log10 PFU per ml in 120 and 90min, with and without soil, respectively. At the same time, when dried on stainless steel surface, MS2 phage was reduced by >4·53 log10 PFU per carrier in 30min under both conditions. On the other hand, C. difficile endospores in suspension were reduced by 2·26 and 3·65 log10 CFU per ml in 120min with and without soiling, respectively. However, on stainless steel surface, maximal reductions of the C. difficile endospores were 0·8 and 1·5 log10 CFU per carrier with and without soiling, respectively, and a maximal reduction of 2·97 log10 CFU per carrier under greenhouse conditions at 24 h. Overall, photoClO2 showed promise as a technology to control HuNoV contamination on environmental surfaces but requires further optimization and testing against C. difficile endospores. Results from this investigation will serve as a model for how to generate and quantify photoClO2 and how to appropriately evaluate this new class of disinfectants against environmentally resilient pathogens: viruses and bacterial endospores.

Antiviral Effects of Lindera obtusiloba Leaf Extract on Murine Norovirus-1 (MNV-1), a Human Norovirus Surrogate, and Potential Application to Model Foods.

Noroviruses are the leading cause of acute gastroenteritis and food poisoning worldwide. In this study, we investigated the anti-noroviral activity of Lindera obtusiloba leaf extract (LOLE) using murine norovirus (MNV-1), a surrogate of human norovirus. Preincubation of MNV-1 with LOLE at 4, 8, or 12 mg/mL for 1 h at 25 °C significantly reduced viral infectivity, by 51.8%, 64.1%, and 71.2%, respectively. Among LOLE single compounds, β-pinene (49.7%), α-phellandrene (26.2%), and (+)-limonene (17.0%) demonstrated significant inhibitory effects on viral infectivity after pretreatment with MNV-1, suggesting that the anti-noroviral effects of LOLE may be due to the synergetic activity of several compounds, with β-pinene as a key molecule. The inhibitory effect of LOLE was tested on the edible surfaces of lettuce, cabbage, and oysters, as well as on stainless steel. After one hour of incubation at 25°C, LOLE (12 mg/mL) pretreatment significantly reduced MNV-1 plaque formation on lettuce (76.4%), cabbage (60.0%), oyster (38.2%), and stainless-steel (62.8%). These results suggest that LOLE effectively inhibits norovirus on food and metal surfaces. In summary, LOLE, including β-pinene, may inactivate norovirus and could be used as a natural agent promoting food safety and hygiene.

Genomic Modeling as an Approach to Identify Surrogates for Use in Experimental Validation of SARS-CoV-2 and HuNoV Inactivation by UV-C Treatment.

Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic that continues to pose significant public health concerns. While research to deliver vaccines and antivirals are being pursued, various effective technologies to control its environmental spread are also being targeted. Ultraviolet light (UV-C) technologies are effective against a broad spectrum of microorganisms when used even on large surface areas. In this study, we developed a pyrimidine dinucleotide frequency based genomic model to predict the sensitivity of select enveloped and non-enveloped viruses to UV-C treatments in order to identify potential SARS-CoV-2 and human norovirus surrogates. The results revealed that this model was best fitted using linear regression with r2 = 0.90. The predicted UV-C sensitivity (D90 – dose for 90% inactivation) for SARS-CoV-2 and MERS-CoV was found to be 21.5 and 28 J/m2, respectively (with an estimated 18 J/m2 obtained from published experimental data for SARS-CoV-1), suggesting that coronaviruses are highly sensitive to UV-C light compared to other ssRNA viruses used in this modeling study. Murine hepatitis virus (MHV) A59 strain with a D90 of 21 J/m2 close to that of SARS-CoV-2 was identified as a suitable surrogate to validate SARS-CoV-2 inactivation by UV-C treatment. Furthermore, the non-enveloped human noroviruses (HuNoVs), had predicted D90 values of 69.1, 89, and 77.6 J/m2 for genogroups GI, GII, and GIV, respectively. Murine norovirus (MNV-1) of GV with a D90 = 100 J/m2 was identified as a potential conservative surrogate for UV-C inactivation of these HuNoVs. This study provides useful insights for the identification of potential non-pathogenic (to humans) surrogates to understand inactivation kinetics and their use in experimental validation of UV-C disinfection systems. This approach can be used to narrow the number of surrogates used in testing UV-C inactivation of other human and animal ssRNA viral pathogens for experimental validation that can save cost, labor and time.

The Mechanical Response and Tolerance of the Anteriorly-Tilted Human Pelvis Under Vertical Loading

Military vehicle underbody blast (UBB) is the cause of many serious injuries in theatre today; however, the effects of these chaotic events on the human body are not well understood. The purpose of this research was to replicate UBB loading conditions on the human pelvis and investigate the resulting response in a controlled laboratory setting. In addition to better understanding the response of the human pelvis to high rate vertical loading, this test series also aimed to identify high rate injury thresholds. Twenty-seven post mortem human surrogate (PMHS) component pelvis tests were completed using the University of Virginia's (UVa) simulated blast rig under a range of loading conditions and postures. Of those tests, 17 were in the anteriorly-tilted posture and used to construct the human injury probability curve. Average seat pan (rigid) accelerations for this subset of tests ranged from 300 to 2400 g over 2 to 3 ms of positive phase duration. Post-test computed tomography (CT) scans and necropsies were performed to determine injuries and revealed a frequent occurrence of anterior and posterior injuries, resulting in unstable pelvis ring fractures. The resulting Human Injury Probability Curve (HIPC) yielded mean forces of 5529, 8516, and 12431 N as measured by mass compensated seat platen loadcells applied through the rigid seat to the bilateral ischium are associated with a 10, 25, and 50% risk for unstable pelvic ring sacrum fractures in an anteriorly-tilted pelvis (28° from vertical), respectively.

Hierarchical process using Brier Score Metrics for lower leg injury risk curves in vertical impact

IntroductionParametric survival models are used to develop injury risk curves (IRCs) from impact tests using postmortem human surrogates (PMHS). Through the consideration of different output variables, input parameters and censoring,...

Monte carlo method for estimating whole-body injury metrics from pedestrian impact simulation results

The goal of the current study was to develop a method to estimate whole-body injury metrics (WBIMs), which measure the overall impact of injuries, using stochastic injury prediction results from a computational human surrogate. First, hospitalized pedestrian data was queried to identify injuries sustained by pedestrians and their frequencies. Second, with consideration for an understanding of injury mechanisms and the capability of the computational human surrogate, the whole-body was divided into 17 body regions. Then, an injury pattern database was constructed for each body region for various maximum abbreviated injury scale (MAIS) levels. Third, a two-step Monte Carlo sampling process was employed to generate N virtual pedestrians with an assigned list of injuries in AIS codes. Then, the expected values of WBIMs such as injury severity score (ISS), probability of death, whole-body functional capacity index (WBFCI), and lost years of life (LYL), were estimated. Lastly, the proposed method was verified using injury information from the inpatient pedestrian database. Also, the proposed method was applied to pedestrian impact simulations with various impact speeds to estimate the probability of death with respect to the impact speed. The probability of death from the proposed method was compared with those from epidemiological studies.The proposed method accurately estimated WBIMs such as ISS and WBFCI using either for a given distribution of injury risk or MAIS levels. The predicted probability of death with respect to the impact speed showed a good correlation with those from the epidemiological study. These results imply that if we have a human surrogate that can predict the risk of injury accurately, we can accurately estimate WBIMs using the proposed method. The proposed method can simplify a vehicle design optimization process by transforming the multi-objective optimization problem into the single-objective one. Lastly, the proposed method can be applied to other human surrogates such as occupant models.

Suitability of pepper mild mottle virus as a human enteric virus surrogate for assessing the efficacy of thermal or free-chlorine disinfection processes by using infectivity assays and enhanced viability PCR

Evaluating the efficacy of disinfection processes to inactivate human enteric viruses is important for the prevention and control of waterborne diseases caused by exposure to those viruses via drinking water. Here, we evaluated the inactivation of two representative human enteric viruses (adenovirus type 40 [AdV] and coxsackievirus B5 [CV]) by thermal or free-chlorine disinfection. In addition, we compared the infectivity reduction ratio of a plant virus (pepper mild mottle virus [PMMoV], a recently proposed novel surrogate for human enteric viruses for the assessment of virus removal by coagulation‒rapid sand filtration and membrane filtration) with that of the two human enteric viruses to assess the suitability of PMMoV as a human enteric virus surrogate for use in thermal and free-chlorine disinfection processes. Finally, we examined whether conventional or enhanced viability polymerase chain reaction (PCR) analysis using propidium monoazide (PMA) or improved PMA (PMAxx) with or without an enhancer could be used as alternatives to infectivity assays (i.e., plaque-forming unit method for AdV and CV; local lesion count assay for PMMoV) for evaluating virus inactivation by disinfection processes. We found that PMMoV was more resistant to heat treatment than AdV and CV, suggesting that PMMoV is a potential surrogate for these two enteric viruses with regard to thermal disinfection processes. However, PMMoV was much more resistant to chlorine treatment compared with AdV and CV (which is chlorine-resistant) (CT value for 4-log10 inactivation: PMMoV, 84.5 mg-Cl2·min/L; CV, 1.15–1.19 mg-Cl2·min/L), suggesting that PMMoV is not useful as a surrogate for these enteric viruses with regard to free-chlorine disinfection processes. For thermal disinfection, the magnitude of the signal reduction observed with PMAxx-Enhancer-PCR was comparable with the magnitude of reduction in infectivity, indicating that PMAxx-Enhancer-PCR is a potential alternative to infectivity assay. However, for free-chlorine disinfection, the magnitude of the signal reduction observed with PMAxx-Enhancer-PCR was smaller than the magnitude of the reduction in infectivity, indicating that PMAxx-Enhancer-PCR underestimated the efficacy of virus inactivation (i.e., overestimated the infectious virus concentration) by chlorine treatment. Nevertheless, among the PCR approaches examined in the present study (PCR alone, PMA-PCR or PMAxx-PCR either with or without enhancer), PMAxx-Enhancer-PCR provided the most accurate assessment of the efficacy of virus inactivation by thermal or free chlorine disinfection processes.