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Background: In preparation for potential clinical development of Ab-01, an antagonistic antibody directed against the IL21R, studies were undertaken to address translational medicine needs that fall into four categories: 1) development of a pharmacodynamic biomarker assay suitable for use in the clinic, 2) demonstration that Ab-01 has the desired biological activity in vitro and in vivo in cynomolgus monkeys, the preferred safety study species, 3) pre-clinical in vivo proof-of-concept that the assay can be used to detect Ab-01 pharmacodynamic (PD) activity in treated subjects, and 4) comprehensive assessment of the agonistic potential of Ab-01 when cross-linked. This report and a recently published companion report address the first three of these needs. The fourth has been addressed in a separate study.Methods: Genes that change RNA expression upon ex vivo rhIL21 stimulation of whole blood were identified in human and cynomolgus monkey. The inhibitory effects of exogenously added Ab-01 were measured ex vivo in human and monkey, and the in vivo inhibitory effects of Ab-01 treatment were measured in monkey.Results: Stimulation of whole human blood for 2 hours with rhIL21 induced robust increases in RNA expression of 6 genes. This response was blocked by Ab-01, indicating that the assay is suitable for measuring Ab-01 activity in blood. rhIL21 induced expression of a similar set of genes in cynomolgus monkey blood. This response was blocked with Ab-01, thus demonstrating that Ab-01 has the desired activity in the species, and that safety studies done in cynomolgus monkeys are relevant. Proof -of-concept for using this assay system to detect PD activity in vivo was generated by measuring the response in monkey blood to ex vivo rhIL21 stimulation before and 5 minutes following in vivo Ab-01 administration.Conclusions: A robust PD biomarker assay suitable for clinical use has been developed in human whole blood. The successful adaptation of the assay to cynomolgus monkeys has enabled the demonstration of Ab-01 activity both in vitro and in vivo in monkey, thus validating the use of this species in safety studies and establishing proof-of-concept for using this PD assay system to aid in dose selection in clinical studies. [ABSTRACT FROM AUTHOR]

Background: Among older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research. The main objective of the Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial (NCT05764733) is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary WL-associated bone loss among 308 older (≥60 years) adults living with an indication for WL and bisphosphonate use., Methods: All participants will receive the same group-mediated dietary intervention targeting 8-10 % WL and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT + +PL); no RT and oral bisphosphonate (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and oral bisphosphonate (RT + +BIS). Total hip areal (a)BMD measured via dual-energy x-ray absorptiometry (DXA) is the primary, powered study outcome. Secondary skeletal outcome measures include femoral neck and lumbar spine aBMD, high resolution peripheral quantitative computed tomography (HRpQCT) bone assessments of the radius and tibia, and biomarkers of bone turnover., Discussion: BEACON will address an understudied, yet important, clinical research question by studying the independent and combined effects of two scalable intervention strategies aimed at optimizing skeletal integrity in older adults undergoing WL., Clinical Trials Registration: NCT05764733., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The bacterium Pseudomonas aeruginosa is an opportunistic pathogen that can cause lung, skin, wound, joint, urinary tract, and eye infections. While P. aeruginosa is known to exhibit a robust competitive response towards other bacterial species, this bacterium is frequently identified in polymicrobial infections where multiple species survive. For example, in prosthetic joint infections (PJIs), P. aeruginosa can be identified along with other pathogenic bacteria including Staphylococcus aureus, Enterococcus faecalis, and Corynebacterium striatum. Here we have explored the survival and behavior of such microbes and find that E. faecalis readily survives culturing with P. aeruginosa while other tested species do not. In each of the tested conditions, E. faecalis growth remained unchanged by the presence of P. aeruginosa, indicating a unique mutualistic interaction between the two species. We find that E. faecalis proximity leads P. aeruginosa to attenuate competitive behaviors as exemplified by reduced production of Pseudomonas quinolone signal (PQS) and pyocyanin. Reduced alkyl quinolones is important to E. faecalis as it will grow in supernatant from a quinolone mutant but not P. aeruginosa wildtype in planktonic culture. The reduced pyocyanin production of P. aeruginosa is attributable to production of ornithine by E. faecalis , which we recapitulate by adding exogenous ornithine to P. aeruginosa monocultures. Similarly, co-culture with an ornithine-deficient strain of E. faecalis leads P. aeruginosa to yield near mono-culture amounts of pyocyanin. Here, we directly demonstrate how notorious pathogens such as P. aeruginosa might persist in polymicrobial infections under the influence of metabolites produced by other bacterial species., Competing Interests: Competing interests The authors declare no competing interest.

Objective: Finite element (FE) reconstructions of motor vehicle crashes using human body models are effective tools for developing a better understanding of occupant kinematics and injuries in real-world lateral crash conditions, but current near-side reconstruction methods are limited by the paucity of full-scale FE vehicle models. The objective of this study was to validate a generic vehicle model equipped with left-side airbags and intrusion capability by simulating a series of near-side crash tests for a range of vehicles and assessing model accuracy using objective evaluation methods., Methods: Moving deformable barrier crash tests were reconstructed for five common vehicle classifications (compact passenger, mid-size passenger, sport utility vehicle, pickup truck, and van) using an updated version of a previously developed simplified vehicle model. Unknown vehicle and intrusion properties (pretensioner force, seatback airbag pressure, curtain airbag pressure, door panel stiffness, ratio of dynamic-to-static intrusion, intrusion velocity, and intrusion scaling factor) were estimated by parameterizing them across 224 simulations per crash test using a Latin hypercube design of experiments. Model accuracy was assessed for 13 anthropomorphic test device signals using the Correlation and Analysis (CORA) objective rating method and injury metric comparisons., Results: Maximum ratings of 0.69, 0.67, 0.52, 0.52, and 0.62 were achieved for the compact passenger, midsize passenger, sport utility vehicle, pickup truck, and van classifications, respectively. On average, the abdomen displayed the most accurate behavior (0.51 ± 0.12), followed by the thorax (0.50 ± 0.10) and head (0.50 ± 0.07). The pelvis displayed the least accurate behavior (0.46 ± 0.18) of any region. Reconstructions overpraedicted injury metrics in all cases., Conclusions: All vehicles achieved "fair" biofidelity ratings and the compact passenger and midsize passenger vehicles achieved "good" biofidelity ratings, validating them for kinematic evaluations with vehicle-to-vehicle nearside crash reconstructions. Regression models were developed for injuries and CORA ratings and can be used to optimize vehicle parameters in future studies.

Opportunistic screening uses existing imaging studies for additional diagnostic insights without imposing further burden on patients. We explore the potential of opportunistic computed tomography (CT) screening for osteoporosis, a condition affecting 500 million people globally and leading to significant health care costs and fragility fractures. Although dual-energy X-ray absorptiometry (DXA) remains the gold standard for diagnosing osteoporosis, > 50% of fractures occur in individuals not screened previously with DXA. With recent advancements in technology, CT has emerged as the most promising tool for opportunistic screening due to its wide use and the ability to provide quantitative measurements of bone attenuation, a surrogate of bone mineral density. This article discusses the technical considerations, calibration methods, and potential benefits of CT for osteoporosis screening. It also explores the role of automation, supervised and unsupervised, in streamlining the diagnostic process, improving accuracy, and potentially developing new biomarkers of bone health. The potential addition of radiomics and genomics is also highlighted, showcasing the synergy between genetic and imaging data for a more comprehensive understanding of osteoporosis pathophysiology and with it possible novel osteoporosis therapies. The future of opportunistic CT screening holds significant promise, with automation and advanced image processing ultimately enhancing patient care, reducing rates of osteoporotic fractures, and improving patient outcomes., Competing Interests: None declared., (Thieme. All rights reserved.)

Extravehicular activities will play a crucial role in lunar exploration on upcoming Artemis missions and may involve astronauts operating a lunar terrain vehicle (LTV) in a standing posture. This study assessed kinematic response and injury risks using an active muscle human body model (HBM) restrained in an upright posture on the LTV by simulating dynamic acceleration pulses related to lunar surface irregularities. Linear accelerations and rotational displacements of 5 lunar obstacles (3 craters; 2 rocks) over 5 slope inclinations were applied across 25 simulations. All body injury metrics were below NASA's injury tolerance limits, but compressive forces were highest in the lumbar (250-550N lumbar, tolerance: 5300N) and lower extremity (190-700N tibia, tolerance: 1350N) regions. There was a strong association between the magnitudes of body injury metrics and LTV resultant linear acceleration (ρ = 0.70-0.81). There was substantial upper body motion, with maximum forward excursion reaching 375 mm for the head and 260 mm for the chest. Our findings suggest driving a lunar rover in an upright posture for these scenarios is a low severity impact presenting low body injury risks. Injury metrics increased along the load path, from the lower body (highest metrics) to the upper body (lowest metrics). While upper body injury metrics were low, increased body motion could potentially pose a risk of injury from flail and occupant interaction with the surrounding vehicle, suit, and restraint hardware., (© 2024. The Author(s).)

The increased use of computational human models in evaluation of safety systems demands greater attention to selected methods in coupling the model to its seated environment. This study assessed the THUMS v4.0.1 in an upright driver posture and a reclined occupant posture. Each posture was gravity settled into an NCAC vehicle model to assess model quality and HBM to seat coupling. HBM to seat contact friction and seat stiffness were varied across a range of potential inputs to evaluate over a range of potential inputs. Gravity settling was also performed with and without constraints on the pelvis to move towards the target H-Point. These combinations resulted in 18 simulations per posture, run for 800 ms. In addition, 5 crash pulse simulations (51.5 km/h delta V) were run to assess the effect of settling time on driver kinematics. HBM mesh quality and HBM to seat coupling metrics were compared at kinetically identical time points during the simulation to an end state where kinetic energy was near zero. A gravity settling time of 350 ms was found to be optimal for the upright driver posture and 290 ms for the reclined occupant posture. This suggests that reclined passengers can be settled for less time than upright passengers, potentially due to the increased contact area. The pelvis constrained approach was recommended for the upright driver posture and was not recommended for the reclined occupant posture. The recommended times were sufficient to gravity settle both postures to match the quality metrics of the 800 ms gravity settled time. Driver kinematics were found to be vary with gravity settling time. Future work will include verifying that these recommendations hold for different HBMs and test modes.

Bacterial communities exhibit complex self-organization that contributes to their survival. To better understand the molecules that contribute to transforming a small number of cells into a heterogeneous surface biofilm community, we studied acellular aggregates, structures seen by light microscopy in Pseudomonas aeruginosa colony biofilms using light microscopy and chemical imaging. These structures differ from cellular aggregates, cohesive clusters of cells important for biofilm formation, in that they are visually distinct from cells using light microscopy and are reliant on metabolites for assembly. To investigate how these structures benefit a biofilm community we characterized three recurrent types of acellular aggregates with distinct geometries that were each abundant in specific areas of these biofilms. Alkyl quinolones (AQs) were essential for the formation of all aggregate types with AQ signatures outside the aggregates below the limit of detection. These acellular aggregates spatially sequester AQs and differentiate the biofilm space. However, the three types of aggregates showed differing properties in their size, associated cell death, and lipid content. The largest aggregate type co-localized with spatially confined cell death that was not mediated by Pf4 bacteriophage. Biofilms lacking AQs were absent of localized cell death but exhibited increased, homogeneously distributed cell death. Thus, these AQ-rich aggregates regulate metabolite accessibility, differentiate regions of the biofilm, and promote survival in biofilms.IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen with the ability to cause infection in the immune-compromised. It is well established that P. aeruginosa biofilms exhibit resilience that includes decreased susceptibility to antimicrobial treatment. This work examines the self-assembled heterogeneity in biofilm communities studying acellular aggregates, regions of condensed matter requiring alkyl quinolones (AQs). AQs are important to both virulence and biofilm formation. Aggregate structures described here spatially regulate the accessibility of these AQs, differentiate regions of the biofilm community, and despite their association with autolysis, correlate with improved P. aeruginosa colony biofilm survival., Competing Interests: The authors declare no conflict of interest.

Force-sensing insoles are wearable technology that offer an innovative way to measure loading outside of laboratory settings. Few studies, however, have utilized insoles to measure daily loading in real-world settings. This is an ancillary study of a randomized controlled trial examining the effect of weight loss alone, weight loss plus weighted vest, or weight loss plus resistance training on bone health in older adults. The purpose of this ancillary study was to determine the feasibility of using force-sensing insoles to collect daily limb loading metrics, including peak force, impulse, and loading rate. Forty-four participants completed a baseline visit of three, 2-minute walking trials while wearing force-sensing insoles. During month two of the intervention, 37 participants wore insoles for 4 days for 8 waking hours each day. At 6-month follow-up, participants completed three, two-minute walking trials and a satisfaction questionnaire. Criteria for success in feasibility was defined as: a) > 60 % recruitment rate; b) > 80 % adherence rate; c) > 75 % of usable data, and d) > 75 % participant satisfaction. A 77.3 % recruitment rate was achieved, with 44 participants enrolled. Participants wore their insoles an average of 7.4 hours per day, and insoles recorded an average of 5.5 hours per day. Peak force, impulse, and loading rate collected at baseline and follow-up were 100 % usable. During the real-world settings, 87.8 % of data was deemed usable with an average of 1200 min/participant. Lastly, average satisfaction was 80.5 %. These results suggest that force-sensing insoles appears to be feasible to capture real-world limb loading in older adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: The objective of this study is to examine the effects of seatback angle, seat rotation, and impact speed on occupant kinematics and injury risk in highly automated vehicles., Methods: The study utilized the Global Human Body Models Consortium midsize male (M50-OS+B) simplified occupant model in a simplified vehicle model (SVM) to simulate frontal crashes. The M50-OS+B model was gravity-settled and belted into the driver and left rear passenger seat. To investigate the effects of seatback angle, seat rotation, and impact speed on occupant kinematics and injury risk in frontal crashes, a design of experiments (DOE) was conducted. The DOE incorporated four seatback angles (13°, 23°, 45°, and 57.5° about vertical), four seat rotation angles (0°, 25°, 45°, and 90°), three impact speeds (25, 35, and 45 kph), and four frontal crash type configurations. All four seatback angles were used with 0° seat rotation, whereas 13° seatback angle was used with the remaining seat rotation configurations because of cabin fit considerations. Injury risks were estimated for the head, neck, shoulder, thorax, pelvis, and lower extremities for both occupants for each simulation (n=588)., Results: Statistically significant differences between all the groups within each independent variable category were observed based on the analysis of variance. HIC-based head injury risk and chest injury risk decreased and femur force for the driver and tibia force for the passenger increased with an increase in seatback angles. The head injury risk increased with seat rotation. All the injury risks increased with an increase in impact speed. The driver airbag was able to safeguard the driver from head injuries for all seat rotations except at 90° of seat rotation., Conclusion: This is the first vehicle modeling study that collectively looked at the effects of seatback angle, seat rotation, and impact speed along with the interaction of occupants on the risk of injury in frontal crashes. The rear passenger experienced higher seatbelt loads than the driver. More reclined seats decreased head and chest injury risk, but increased driver femur injury risk and rear passenger tibia injury risk. Results underscore the necessity for additional anti-submarining mechanisms and driver airbag designs adapted for the anticipated occupant positions.

Spinal injuries are a concern for automotive applications, requiring large parametric studies to understand spinal injury mechanisms under complex loading conditions. Finite element computational human body models (e.g. Global Human Body Models Consortium (GHBMC) models) can be used to identify spinal injury mechanisms. However, the existing GHBMC detailed models (with high computational time) or GHBMC simplified models (lacking vertebral fracture prediction capabilities) are not ideal for studying spinal injury mechanisms in large parametric studies. To overcome these limitations, a modular 50 th percentile male simplified occupant model combining advantages of both the simplified and detailed models, M50-OS + DeformSpine, was developed by incorporating the deformable spine and 3D neck musculature from the detailed GHBMC model M50-O (v6.0) into the simplified GHBMC model M50-OS (v2.3). This new modular model was validated against post-mortem human subject test data in four rigid hub impactor tests and two frontal impact sled tests. The M50-OS + DeformSpine model showed good agreement with experimental test data with an average CORrelation and Analysis (CORA) score of 0.82 for the hub impact tests and 0.75 for the sled impact tests. CORA scores were statistically similar overall between the M50-OS + DeformSpine (0.79 ± 0.11), M50-OS (0.79 ± 0.11), and M50-O (0.82 ± 0.11) models ( p  > 0.05). This new model is computationally 6 times faster than the detailed M50-O model, with added spinal injury prediction capabilities over the simplified M50-OS model.

Motor vehicle crash (MVC) occupants routinely get a computed tomography (CT) scan to screen for internal injury, and this CT can be leveraged to opportunistically derive bone mineral density (BMD). This study aimed to develop and validate a method to measure pelvic BMD in CT scans without a phantom, and examine associations of pelvic BMD with age and pelvic fracture incidence in seriously injured MVC occupants from the Crash Injury Research and Engineering Network (CIREN) study. A phantom-less muscle-fat calibration technique to measure pelvic BMD was validated using 45 quantitative CT scans with a bone calibration phantom. The technique was then used to measure pelvic BMD from CT scans of 252 CIREN occupants (ages 16+) in frontal MVCs who had sustained either abdominal or pelvic injury. Pelvic BMD was analyzed in relation to age and pelvic fracture incidence. In the validation set, phantom-based calibration vs. phantom-less muscle-fat calibration yielded similar BMD values at the anterior superior iliac spine (ASIS; R 2  = 0.95, p < 0.001) and iliac crest (R 2  = 0.90, p < 0.001). Pelvic BMD was measured in 150 female and 102 male CIREN occupants aged 16-89, and 25% of these occupants sustained pelvic fracture. BMD at the ASIS and iliac crest declined with age (p < 0.001). For instance, iliac crest BMD decreased an average of 25 mg/cm 3 per decade of age. The rate of iliac crest BMD decline was 7.6 mg/cm 3 more per decade of age in occupants with pelvic fracture compared to those not sustaining pelvic fracture. Findings suggest pelvic BMD may be a contributing risk factor for pelvic fracture in MVCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rhamnolipids are surfactants produced by many Pseudomonad bacteria, including the species Pseudomonas aeruginosa . These rhamnolipids are known to aid and enable numerous phenotypic traits that improve the survival of the bacteria that make them. These surfactants are also important for industrial products ranging from pharmaceuticals to cleaning supplies to cosmetics, to name a few. Rhamnolipids have structural diversity that leads to an array of congeners; however, little is known about the localization and distribution of these congeners in two-dimensional space. Differential distribution of congeners can reduce the uniformity of applications in industrial settings and create heterogeneity within biological communities. We examined the distribution patterns of combinations of rhamnolipids in commercially available mixtures, cell-free spent media, and colony biofilms using mass spectrometry. We found that even in the absence of cells, congeners exhibit different distribution patterns, leading to different rhamnolipid congener distributions on a surface. Congeners with shorter fatty acid chains were more centrally located, while longer chains were more heterogeneous and distally located. We found that congeners with similar structures can distribute differently. Within developing colony biofilms, we found rhamnolipid distribution patterns differed from cell-free environments, lacking simple trends noted in cell-free environments. Most strikingly, we found the distribution patterns of individual congeners in the colony biofilms to be diverse. We note that the congener distribution is far from homogeneous but composed of numerous local microenvironments of varied rhamnolipid congener composition.

The objective of this study was to assess the ability of finite element human body models (FEHBMs) and Anthropometric Test Device (ATD) models to estimate occupant injury risk by comparing it with field-based injury risk in far-side impacts. The study used the Global Human Body Models Consortium midsize male (M50-OS+B) and small female (F05-OS+B) simplified occupant models with a modular detailed brain, and the ES-2Re and SID-IIs ATD models in the simulated far-side crashes. A design of experiments (DOE) with a total of 252 simulations was conducted by varying lateral ΔV (10-50kph; 5kph increments), the principal direction of force (PDOF 50°, 60°, 65°, 70°, 75°, 80°, 90°), and occupant models. Models were gravity-settled and belted into a simplified vehicle model (SVM) modified for far-side impact simulations. Acceleration pulses and vehicle intrusion profiles used for the DOE were generated by impacting a 2012 Camry vehicle model with a mobile deformable barrier model across the 7 PDOFs and 9 lateral ΔV's in the DOE for a total of 63 additional simulations. Injury risks were estimated for the head, chest, lower extremity, pelvis (AIS 2+; AIS 3+), and abdomen (AIS 3+) using logistic regression models. Combined AIS 3+ injury risk for each occupant was calculated using AIS 3+ injury risk estimations for the head, chest, abdomen, and lower extremities. The injury risk calculated using computational models was compared with field-based injury risk derived from NASS-CDS by calculating their correlation coefficient. The field-based injury risk was calculated using risk curves that were created based on real-world crash data in a previous study (Hostetler et al., 2020). Occupant age (40 years), seatbelt use (belted occupant), collision deformation classification, lateral ΔV, and PDOF of the crash event were used in these curves to estimate field injury risk. Large differences in the kinematics were observed between HBM and ATD models. ATD models tended to overestimate risk in almost every case whereas HBMs yielded better risk estimates overall. Chest and lower extremity risks were the least correlated with field injury risk estimates. The overall risk of AIS 3+ injury risk was the strongest comparison to the field data-based risk curves. The HBMs were still not able to capture all the variance but future studies can be carried out that are focused on investigating their shortfalls and improving them to estimate injury risk closer to field injury risk in far-side crashes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F. Scott Gayzik and Matthew Davis are members and Ashley A. Weaver is a consultant of Elemance, LLC, which distributes academic and commercial licenses for the use of GHBMC-owned computational human body models., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Traditionally, weight loss (WL) trials utilize dual energy X-ray absorptiometry (DXA) to measure lean mass. This method assumes lean mass, as the sum of all non-bone and non-fat tissue, is a reasonable proxy for muscle mass. In contrast, the D 3 -creatine (D 3 Cr) dilution method directly measures whole body skeletal muscle mass, although this method has yet to be applied in the context of a geriatric WL trial. The purpose of this project was to (1) describe estimates of change and variability in D 3 Cr muscle mass in older adults participating in an intentional WL intervention and (2) relate its change to other measures of body composition as well as muscle function and strength., Methods: The INVEST in Bone Health trial (NCT04076618), used as a scaffold for this ancillary pilot project, is a three-armed, 12-month randomized, controlled trial designed to determine the effects of resistance training or weighted vest use during intentional WL on a battery of musculoskeletal health outcomes among 150 older adults living with obesity. A convenience sample of 24 participants (n = 8/arm) are included in this analysis. At baseline and 6 months, participants were weighed, ingested a 30 mg D 3 Cr tracer dose, provided a fasted urine sample 3-6 days post-dosage, underwent DXA (total body fat and lean masses, appendicular lean mass) and computed tomography (mid-thigh and trunk muscle/intermuscular fat areas) scans, and performed 400-m walk, stair climb, knee extensor strength, and grip strength tests., Results: Participants were older (68.0 ± 4.4 years), mostly White (75.0%), predominantly female (66.7%), and living with obesity (body mass index: 33.8 ± 2.7 kg/m 2 ). Six month total body WL was -10.3 (95% confidence interval, CI: -12.7, -7.9) kg. All DXA and computed tomography-derived body composition measures were significantly decreased from baseline, yet D 3 Cr muscle mass did not change [+0.5 (95% CI: -2.0, 3.0) kg]. Of muscle function and strength measures, only grip strength significantly changed [+2.5 (95% CI: 1.0, 4.0) kg] from baseline., Conclusions: Among 24 older adults, significant WL with or without weighted vest use or resistance training over a 6-month period was associated with significant declines in all bioimaging metrics, while D 3 Cr muscle mass and muscle function and strength were preserved. Treatment assignment for the trial remains blinded; therefore, full interpretation of these findings is limited. Future work in this area will assess change in D 3 Cr muscle mass by parent trial treatment group assignment in all study participants., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Rib fracture(s) occurs in 85% of blunt chest trauma cases. Increasing evidence supports that surgical intervention, particularly for multiple fractures, may improve outcomes. Thoracic morphology diversity across ages and sexes is important to consider in the design and use of surgical intervention devices in chest trauma. However, research on non-average thoracic morphology is lacking., Methods: The rib cage was segmented from patient computed tomography (CT) scans to create 3D point clouds. These point clouds were uniformly oriented and chest height, width, and depth were measured. Size categorization was determined by grouping each dimension into small, medium, and large tertiles. From small and large size combinations, subgroups were extracted to develop thoracic 3D models of the rib cage and surrounding soft tissue., Results: The study population included 141 subjects (48% male) ranging from age 10-80 with ∼20 subjects/age decade. Mean chest volume increased with age by 26% from the age groups 10-20 to 60-70, with 11% of this increase occurring between the youngest groups of 10-20 and 20-30. Across all ages, chest dimensions were ∼10% smaller in females and chest volume was highly variable (SD: ±3936.5 cm 3 ). Representative thoracic models of four males (ages 16, 24, 44, 48) and three females (ages 19, 50, 53) were developed to characterize morphology associated with combinations of small and large chest dimensions., Conclusions: The seven models developed cover a broad range of non-average thoracic morphologies and can serve as a basis for informing device design, surgical planning, and injury risk assessments., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study compared two morphing techniques (and their serial combination) to create subject-specific finite element models of 15 astronaut vertebrae. Surface deviations of the morphed models were compared against subject geometries extracted from medical images. The optimal morphing process yielded models with minimal difference in root-mean-square (RMS) deviation (C3, 0.52 ± 0.14 mm; T3, 0.34 ± 0.04 mm; L1, 0.59 ± 0.16 mm) of the subject's vertebral geometry. <1% of model elements failed quality checks and compression simulations ran to completion. This research lays the foundation for the development of subject-specific finite element models to quantify musculoskeletal changes and injury risk from spaceflight.

Background: Despite recognized improvements in obesity-related comorbidities, mounting evidence implicates surgical weight loss in the onset of skeletal fragility. Sleeve gastrectomy (SG) is the most commonly performed bariatric procedure and is associated with 3-7% axial bone loss in the year following surgery. Bisphosphonates are FDA-approved medications for the prevention and treatment of age-related bone loss and may represent a strategy to reduce bone loss following SG surgery., Methods: The Strategies to Reduce the Onset of Sleeve Gastrectomy Associated Bone Loss (STRONG BONES) trial (NCT04922333) is designed to definitively test whether monthly administration of the bisphosphonate, risedronate, for six months can effectively counter SG-associated bone loss. Approximately 120 middle-aged and older (≥40 years) SG patients will be randomized to six months of risedronate or placebo treatment, with skeletal outcomes assessed at baseline, six, and 12-months post-surgery. The primary outcome of the trial is 12-month change in total hip areal bone mineral density (aBMD), measured by dual energy x-ray absorptiometry (DXA). This will be complemented by DXA-acquired aBMD assessment at other skeletal sites and quantitative computed tomography (QCT) derived changes in bone quality. Change in muscle mass and function will also be assessed, as well as biomarkers of bone health, turnover, and crosstalk, providing mechanistic insight into intervention-related changes to the bone-muscle unit., Discussion: Results from the STRONG BONES trial have the potential to influence current clinical practice by determining the ability of bisphosphonate use to mitigate bone loss and concomitant fracture risk in middle-aged and older SG patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

While astronauts may pilot future lunar landers in a standing posture, the response of the human body under lunar launch and landing-related dynamic loading conditions is not well understood. It is important to consider the effects of active muscles under these loading conditions as muscles stabilize posture while standing. In the present study, astronaut response for a piloted lunar mission in a standing posture was simulated using an active human body model (HBM) with a closed-loop joint-angle based proportional integral derivative controller muscle activation strategy and compared with a passive HBM to understand the effects of active muscles on astronaut body kinematics and injury risk. While head, neck, and lumbar spine injury risk were relatively unaffected by active muscles, the lower extremity injury risk and the head and arm kinematics were significantly changed. Active muscle prevented knee-buckling and spinal slouching and lowered tibia injury risk in the active vs. passive model (revised tibia index: 0.02-0.40 vs. 0.01-0.58; acceptable tolerance: 0.43). Head displacement was higher in the active vs. passive model (11.6 vs. 9.0 cm forward, 6.3 vs. 7.0 cm backward, 7.9 vs. 7.3 cm downward, 3.7 vs. 2.4 cm lateral). Lower arm movement was seen with the active vs. passive model (23 vs. 35 cm backward, 12 vs. 20 cm downward). Overall simulations suggest that the passive model may overpredict injury risk in astronauts for spaceflight loading conditions, which can be improved using the model with active musculature., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Introduction/aims: Although muscle structure measures from magnetic resonance imaging (MRI) have been used to assess disease severity in muscular dystrophies, little is known about how these measures are affected in myotonic dystrophy type 2 (DM2). We aim to characterize lower extremity muscle fat fraction (MFF) as a potential biomarker of disease severity, and evaluate its relationship with motor performance in DM2., Methods: 3-Tesla MRIs were obtained from nine patients with DM2 and six controls using a T1W-Dixon protocol. To calculate MFF, muscle volumes were segmented from proximal, middle, and distal regions of the thigh and calf. Associations between MFF and motor performance were calculated using Spearman's correlations (ρ)., Results: Mean age of DM2 participants was 62 ± 11 y (89% female), and mean symptom duration was 20 ± 12 y. Compared to controls, the DM2 group had significantly higher MFF in the thigh and the calf segments (p-value = .002). The highest MFF at the thigh in DM2 was located in the posterior compartment (39.7 ± 12.9%) and at the calf was the lateral compartment (31.5 ± 8.7%). In the DM2 group, we found a strong correlation between the posterior thigh MFF and the 6-min walk test (ρ = -.90, p-value = .001). The lateral calf MFF was also strongly correlated with the step test (ρ = -0.82, p-value = .006)., Discussion: Our pilot data suggest a potential correlation between lower extremity MFF and some motor performance tests in DM2. Longitudinal studies with larger sample sizes are required to validate MFF as a marker of disease severity in DM2., (© 2023 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Astronauts may pilot a future lunar lander in a standing or upright/reclined seated posture. This study compared kinematics and injury risk for the upright/reclined (30°; 60°) seated vs. standing postures for lunar launch/landing using human body modeling across 30 simulations. While head metrics for standing and upright seated postures were comparable to 30 cm height jumps, those of reclined postures were closer to 60 cm height jumps. Head linear acceleration for 60° reclined posture in the 5 g/10 ms pulse exceeded NASA's tolerance (10.1 g; tolerance: 10 g). Lower extremity metrics exceeding NASA's tolerance in the standing posture (revised tibia index: 0.36-0.53; tolerance: 0.43) were lowered in seated postures (0.00-0.04). Head displacement was higher in standing vs. seated (9.0 cm vs. 2.4 cm forward, 7.0 cm vs. 1.3 cm backward, 2.1 cm vs. 1.2 cm upward, 7.3 cm vs. 0.8 cm downward, 2.4 cm vs. 3.2 cm lateral). Higher arm movement was seen with seated vs. standing (40 cm vs. 25 cm forward, 60 cm vs. 15 cm upward, 30 cm vs. 20 cm downward). Pulse-nature contributed more than 40% to the injury metrics for seated postures compared to 80% in the standing posture. Seat recline angle contributed about 22% to the injury metrics in the seated posture. This study established a computational methodology to simulate the different postures of an astronaut for lunar landings and generated baseline injury risk and body kinematics data., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Little is known about the effect of exercise modality during a dietary weight loss program on muscle size and quality, as measured by computed tomography (CT). Even less is known about how CT-derived changes in muscle track with changes in volumetric bone mineral density (vBMD) and bone strength., Methods: Older adults (66 ± 5 years, 64 % women) were randomized to 18-months of diet-induced weight loss (WL), WL with aerobic training (WL + AT), or WL with resistance training (WL + RT). CT-derived muscle area, radio-attenuation and intermuscular fat percentage at the trunk and mid-thigh were determined at baseline (n = 55) and 18-month follow-up (n = 22-34), and changes were adjusted for sex, baseline value, and weight lost. Lumbar spine and hip vBMD and finite element-derived bone strength were also measured., Results: After adjustment for the weight lost, muscle area losses at the trunk were -7.82 cm 2 [-12.30, -3.35] for WL, -7.72 cm 2 [-11.36, -4.07] for WL + AT, and -5.14 cm 2 [-8.65, -1.63] for WL + RT (p < 0.001 for group differences). At the mid-thigh, decreases were -6.20 cm 2 [-10.39, -2.02] for WL, -7.84 cm 2 [-11.19, -4.48] for WL + AT, and -0.60 cm 2 [-4.14, 2.94] for WL + RT; this difference between WL + AT and WL + RT was significant in post-hoc testing (p = 0.01). Change in trunk muscle radio-attenuation was positively associated with change in lumbar bone strength (r = 0.41, p = 0.04)., Conclusions: WL + RT better preserved muscle area and improved muscle quality more consistently than WL + AT or WL alone. More research is needed to characterize the associations between muscle and bone quality in older adults undertaking weight loss interventions., Competing Interests: Declaration of competing interest The authors declare no relevant conflicts of interest. Data that support the findings of this study are available from the corresponding author upon reasonable request., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Active muscles play an important role in postural stabilization, and muscle-induced joint stiffening can alter the kinematic response of the human body, particularly that of the lower extremities, under dynamic loading conditions. There are few full-body human body finite element models with active muscles in a standing posture. Thus, the objective of this study was to develop and validate the M50-PS+Active model, an average-male simplified human body model in a standing posture with active musculature. The M50-PS+Active model was developed by incorporating 116 skeletal muscles, as one-dimensional beam elements with a Hill-type material model and closed-loop Proportional Integral Derivative (PID) controller muscle activation strategy, into the Global Human Body Models Consortium (GHBMC) simplified pedestrian model M50-PS. The M50-PS+Active model was first validated in a gravity standing test, showing the effectiveness of the active muscles in maintaining a standing posture under gravitational loading. The knee kinematics of the model were compared against volunteer kinematics in unsuited and suited step-down tests from NASA's active response gravity offload system (ARGOS) laboratory. The M50-PS+Active model showed good biofidelity with volunteer kinematics with an overall CORA score of 0.80, as compared to 0.64 (fair) in the passive M50-PS model. The M50-PS+Active model will serve as a useful tool to study the biomechanics of the human body in vehicle-pedestrian accidents, public transportation braking, and space missions piloted in a standing posture., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Purpose: With extravascular implantable cardioverter defibrillator leads placed beneath the sternum, it is important to quantify heart motion relative to the rib cage with postural changes and respiration., Methods: MRI scans from five males and five females were collected in upright and supine postures at end inspiration [n = 10 each]. Left and right decubitus [n = 8 each] and prone [n = 5] MRIs at end inspiration and supine MRIs at end expiration [n = 5] were collected on a subset. Four cardiothoracic measurements, six cardiac measurements, and six cardiac landmarks were collected to measure changes across different postures and stages of respiration., Results: The relative location of the LV apex to the nearest intercostal space was significantly different between the supine and decubitus postures (average ± SD difference: - 15.7 ± 11.4 mm; p < 0.05). The heart centroid to xipho-sternal junction distance was 9.7 ± 7.9 mm greater in the supine posture when compared to the upright posture (p < 0.05). Cardiac landmark motion in the lateral direction was largest due to postural movement (range 23-50 mm) from the left decubitus to the right decubitus posture, and less influenced by respiration (5-17 mm). Caudal-cranial displacement was generally larger due to upright posture (13-23 mm caudal) and inspiration (7-20 mm cranial)., Conclusions: This study demonstrates that the location of the heart with respect to the rib cage varies with posture and respiration. The gravitational effects of postural shifts on the heart position are roughly 2-3 times larger than the effects of normal respiration., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

A sensitivity analysis for loading conditions and muscle deconditioning on astronaut response for spaceflight transient accelerations was carried out using a mid-size male human body model with active musculature. The model was validated in spaceflight-relevant 2.5-15 g loading magnitudes in seven volunteer tests, showing good biofidelity (CORA: 0.69). Sensitivity analysis was carried out in simulations varying pulse magnitude (5, 10, and 15 g), rise time (32.5 and 120 ms), and direction (10 directions: frontal, rear, vertical, lateral, and their combination) along with muscle size change (± 15% change) and responsiveness (pre-braced, relaxed, vs. delayed response) changes across 600 simulations. Injury metrics were most sensitive to the loading direction (50%, partial-R 2 ) and least sensitive to muscle size changes (0.2%). The pulse magnitude also had significant effect on the injury metrics (16%), whereas muscle responsiveness (3%) and pulse rise time (2%) had only slight effects. Frontal and upward loading directions were the worst for neck, spine, and lower extremity injury metrics, whereas rear and downward directions were the worst for head injury metrics. Higher magnitude pulses and pre-bracing also increased the injury risk., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Despite robust weight loss and cardiometabolic benefit, lean mass loss following sleeve gastrectomy (SG) confers health risk. Bisphosphonates are a potential therapeutic agent for lean mass maintenance. Thus, our objective was to explore the effect of six months of risedronate (vs placebo) on change in dual energy x-ray absorptiometry (DXA) and computed tomography (CT) derived lean mass metrics in the year following SG., Methods: 24 SG patients were randomized to six months of 150 mg oral risedronate or placebo capsules (NCT03411902). Body composition was assessed at baseline and six months with optional 12-month follow-up using whole-body DXA and CT at the lumbar spine and mid-thigh. Group treatment effects and 95% CIs were generated from a mixed model using contrast statements at six and 12 months, adjusted for baseline values., Results: Of 24 participants enrolled [55.7±6.7 years (mean±SD), 79% Caucasian, 83% women, body mass index (BMI) 44.7±6.3kg/m 2 ], 21 returned for six-month testing, and 14 returned for 12-month testing. Six-month weight loss was -16.3 kg (-20.0, -12.5) and -20.9 kg (-23.7, -18.1) in the risedronate and placebo groups, respectively ( p =.057). Primary analysis at six-months revealed a non-significant sparing of appendicular lean mass in the risedronate group compared to placebo [-1.2 kg (-2.3, -0.1) vs -2.1 kg (-3.0, -1.2)]; p =.20. By 12-months, the risedronate group displayed no change in appendicular lean mass from baseline [-0.5 kg (-1.5, 0.6)]; however, the placebo group experienced significantly augmented loss [-2.9 kg (-3.6, -2.1)]., Conclusion: Pilot data indicate risedronate treatment may mitigate appendicular lean mass loss following SG. Further study is warranted.

During future lunar missions, astronauts may be required to pilot vehicles while standing, and the associated kinematic and injury response is not well understood. In this study, we used human body modeling to predict unsuited astronaut kinematics and injury risk for piloted lunar launches and landings in the standing posture. Three pulses (2-5 g; 10-150 ms rise times) were applied in 10 directions (vertical; ± 10-degree offsets) for a total of 30 simulations. Across all simulations, motion envelopes were computed to quantify displacement of the astronaut's head (max 9.0 cm forward, 7.0 cm backward, 2.1 cm upward, 7.3 cm downward, 2.4 cm lateral) and arms (max 25 cm forward, 35 cm backward, 15 cm upward, 20 cm downward, 20 cm lateral). All head, neck, lumbar, and lower extremity injury metrics were within NASA's tolerance limits, except tibia compression forces (0-1543 N upper tibia; 0-1482 N lower tibia; tolerance-1350 N) and revised tibia index (0.04-0.58 upper tibia; 0.03-0.48 lower tibia; tolerance-0.43) for the 2.7 g/150 ms pulse. Pulse magnitude and duration contributed over 80% to the injury metric values, whereas loading direction contributed less than 3%. Overall, these simulations suggest piloting a lunar lander vehicle in the standing posture presents a tibia injury risk which is potentially outside NASA's acceptance limits and warrants further investigation., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Eleven Crash Injury Research and Engineering Network (CIREN) frontal crashes were reconstructed using a novel, time-efficient methodology involving a simplified vehicle model. Kinematic accuracy was assessed using novel kinematic scores between 0-1 and chest injury was assessed using literature-defined injury metric time histories. The average kinematic score across all simulations was 0.87, indicating good kinematic accuracy. Time histories for chest compression, rib strain, shoulder belt force, and steering column force discerned the most causative components of chest injury in all cases. Abbreviated Injury Scale (AIS) 2+ and AIS 3+ chest injury risk functions using belt force identified chest injury with 81.8% success.

Background: Advanced automatic crash notification (AACN) can improve triage decision-making by using vehicle telemetry to alert first responders of a motor vehicle crash and estimate an occupant's likelihood of injury. The objective was to develop an AACN algorithm to predict the risk that a pediatric occupant is seriously injured and requires treatment at a Level I or II trauma center., Methods: Based on 3 injury facets (severity; time sensitivity; predictability), a list of Target Injuries associated with a child's need for Level I/II trauma center treatment was determined. Multivariable logistic regression of motor vehicle crash occupants was performed creating the pediatric-specific AACN algorithm to predict risk of sustaining a Target Injury. Algorithm inputs included: delta-v, rollover quarter-turns, belt status, multiple impacts, airbag deployment, and age. The algorithm was optimized to achieve under-triage ≤5% and over-triage ≤50%. Societal benefits were assessed by comparing correctly triaged motor vehicle crash occupants using the AACN algorithm against real-world decisions., Results: The pediatric AACN algorithm achieved 25% to 49% over-triage across crash modes, and under-triage rates of 2% for far-side, 3% for frontal and near-side, 8% for rear, and 14% for rollover crashes. Applied to real-world motor vehicle crashes, improvements of 59% in under-triage and 45% in over-triage are estimated: more appropriate triage of 32,320 pediatric occupants annually., Conclusions: This AACN algorithm accounts for pediatric developmental stage and will aid emergency personnel in correctly triaging pediatric occupants after a motor vehicle crash. Once incorporated into the trauma triage network, it will increase triage efficiency and improve patient outcomes., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Prolonged microgravity results in muscle atrophy, especially among the anti-gravity spinal muscles. How individual paravertebral muscle groups change in size and composition with spaceflight needs further exploration. This study investigates lumbar spine musculature changes among six crewmembers on long-duration space missions using non-invasive measurement of muscle changes with magnetic resonance imaging (MRI). Pre- and post-flight lumbar images were analyzed for changes in cross-sectional area, volume, and fat infiltration of the psoas (PS), quadratus lumborum (QL), and paraspinal [erector spinae and multifidus (ES + MF)] muscles using mixed models. Crewmembers used onboard exercise equipment, including a cycle ergometer (CEVIS), treadmill (T2/COLBERT), and the advanced resistive exercise device (ARED). Correlations were used to assess muscle changes related to exercise modality. There was substantial variability in muscle changes across crewmembers but collectively a significant decrease in paraspinal area (- 9.0 ± 4.8%, p = 0.04) and a significant increase in QL fat infiltration (7.3 ± 4.1%, p = 0.05). More CEVIS time may have protected against PS volume loss (p = 0.05) and PS fat infiltration (p < 0.01), and more ARED usage may have protected against ES + MF volume loss (p = 0.05). Crewmembers using modern onboard exercise equipment may be less susceptible to muscle changes. However, variability between crewmembers and muscle size and quality losses suggest additional research is needed to ensure in-flight countermeasures preserve muscle health., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Objective: The objective was to develop a disability-based metric for quantifying disability rates as a result of motor vehicle crash (MVC) spine injuries and compare functional outcomes between pediatric and adult subgroups., Methods: Disability rate was quantified using Functional Independence Measure (FIM) scores within the National Trauma Data Bank-Research Data System for the top 95% most frequent Abbreviated Injury Scale (AIS) 3 spine injuries (14 unique injuries). Pediatric (7-18 years), young adult (19-45 years), middle-aged adult (46-65 years), and older adult (66+ years) MVC occupants with FIM scores available and at least one of the 14 spine injuries were included. FIM scores of 1 or 2 at time of discharge were used to define disability and correspond to full functional or modified dependence in self-feeding, locomotion, and/or verbal expression. Disability rate was evaluated on a per injury basis for each AIS 3 spine injury and calculated as the proportion of cases associated with disability (i.e. FIM of 1 or 2) out of the total cases of that particular injury. Disability rates were calculated with and without the exclusion of cases with severe co-injuries (AIS 4+) to minimize bias from additional non-spinal injuries that could have contributed to disability. Associations between adjusted disability rates and existing mortality rates were investigated., Results: Locomotion impairment alone was the most frequent disability type for the top 14 AIS 3 spine injuries (7 cervical, 4 thoracic, and 3 lumbar) across all age groups and spine regions. Adjusted and unadjusted disability rates ranged from 0-69%. Adjusted disability rates increased with age: 14.8 ± 10% (mean ± SD) in pediatrics to 16.2 ± 6.6% (young adults), 29.2 ± 10.9% (middle-aged adults), and 45.0 ± 12.2% (older adults). Among all adult populations, adjusted mortality and disability rates were positively correlated ( R 2 >0.24), with disability rates consistently greater than corresponding mortality rates., Conclusions: Older adults had significantly greater disability rates associated with MVC spine injuries across all spinal regions. MVC disability rates for pediatrics were considerably lower. Overall, rates of mortality were significantly lower than rates of disability. The adjusted disability rates developed can supplement existing injury metrics by accounting for age- and location-specific functional implications of MVC spine injuries.

Objective: The objective of this study is to generate age targeted versions of the male and female Global Human Body Models Consortium (GHBMC) occupant human body models (HBMs), to validate each in frontal impacts, and to assess rib fracture probability of each., Methods: Six age targeted models were developed based on the GHBMC average male and small female occupant models (M50-O v6.0 and F05-O v6.0, respectively). All age targeted models were modified to represent population means for height, weight, shape, and relevant material properties. The thin plate spline method was used to morph models, and material properties were modified using available literature. Validation focused on chest response. Models were evaluated in a rigid body frontal chest impact at 6.7 m/s. Furthermore, the male and female age targeted models were evaluated against published data from 40 km/hr and 30 km/hr frontal sled tests respectively., Results: Chest deflections and landmark kinematics reasonably matched the respective corridors in the M50-O and F05-O aged models. Regional probability of rib fracture was assessed using probabilistic methods based on cortex strain. Increasing rib fracture with age was observed in both impacts for both sexes. For the rigid chest impact, the M50-O 70YO resulted in 10 ribs exceeding 50% probability of fracture whereas the younger ages reported 4 to 6 ribs exceeding the same probability. In the same simulation, the F05-O 70YO resulted in 8 regions exceeding 50% probability of rib fracture as opposed to 3 and 0 such regions at the youngest ages. Sled simulation demonstrated similar trends. The 70YO age adjusted models best aligned with the reported extent of fractures from the referenced PMHS studies, which tend to be composed of subjects of advanced age., Conclusions: Age targeted HBMs demonstrated increased fracture probability with age when subjected to equivalent impacts. Gross model kinematics approximate PMHS data but showed little difference between targeted age models. The findings indicate that while gross kinematics are unaffected by age-targeting models, such models can capture trends of increased thoracic injury risk observed in experimental and field studies, and further suggest their potential use to target interventions for vulnerable driving populations, such as older adults.

Objective: As obesity rates climb, it is important to study its effects on motor vehicle safety due to differences in restraint interaction and biomechanics. Previous studies have shown that an abdominal seatbelt sign (referred hereafter as seatbelt sign) sustained from motor vehicle crashes (MVCs) is associated with abdominal trauma when located above the anterior superior iliac spine (ASIS). This study investigates whether placement of the lap belt causing a seatbelt sign is associated with abdominal organ injury in occupants with increased body mass index (BMI). We hypothesized that higher BMI would be associated with a higher incidence of superior placement of the lap belt to the ASIS level, and a higher incidence of abdominal organ injury., Methods: A retrospective data analysis was performed using 230 cases that met inclusion criteria (belted occupant in a frontal collision that sustained at least one abdominal injury) from the Crash Injury Research and Engineering Network (CIREN) database. Computed tomography (CT) scans were rendered to visualize fat stranding to determine the presence of a seatbelt sign. 146 positive seatbelt signs were visualized. ASIS level was measured by adjusting the transverse slice of the CT to the visualized ASIS level, which was used to determine seatbelt sign location as superior, on, or inferior to the ASIS., Results: Obese occupants had a significantly higher incidence of superior belt placement (52%) vs on-ASIS placement (24%) compared to their normal (27% vs 67%) BMI counterparts (p < 0.001). Notable trends included obese occupants with superior placement having less abdominal organ injury incidence than those with on-ASIS belt placement (42% superior placement vs 55% on-ASIS). In non-obese occupants, there was a higher incidence of abdominal organ injury with superior lap belt placement compared to on-ASIS placement counterparts (Normal BMI: 62% vs 41%, Overweight: 57% vs 43%)., Conclusions: In CIREN occupants with abdominal injury, those with obesity are more prone to positioning the lap belt superior to the ASIS, though the impact on abdominal injury incidence remains a key point for continued exploration into how occupant BMI affects crash safety and belt design.

Objectives: Quantify the independent and combined effects of abdominal muscle quantity and lumbar bone mineral density (BMD) on injury risk and in-hospital outcomes in severely injured motor vehicle crash (MVC) occupants ages 50 and older. Methods: Skeletal muscle area measurements of MVC occupants were obtained through semi-automated segmentation of an axial computed tomography (CT) slice at the L3 vertebra. An occupant height-normalized Skeletal Muscle Index (SMI) was calculated - a defining metric of sarcopenia and low muscle mass (sarcopenia thresholds: <38.5 cm 2 /m 2 females; <52.4 cm 2 /m 2 males). Lumbar BMD was obtained using a validated, phantomless CT calibration method (osteopenia threshold: <145 mg/cm 3 ). SMI and BMD values were used to categorize occupants, and logistic regression was used to associate sarcopenia, osteopenia, and osteosarcopenia predictors to injury outcomes (e.g., Injury Severity Score (ISS), maximum Abbreviated Injury Scale (MAIS) score, fractures) and hospital outcomes (e.g., length of stay, ICU days). Results: Of the 336 occupants, 210 (63%) were female (mean ± SD: age 66.3 ± 10.6). SMI was 41.7 ± 8.0 cm 2 /m 2 in females and 51.2 ± 10.8 cm 2 /m 2 in males. Based on SMI, 40% of females and 55% of males were classified as sarcopenic. BMD was 163.2 ± 38.3 mg/cm 3 in females and 164.1 ± 35.4 mg/cm 3 in males, with 41% of females and 33% of males classified as osteopenic. Prevalence of both conditions (osteosarcopenia) was similar between females (21%) and males (22%). Incidence of low SMI and BMD increased with age. Sarcopenic individuals were less likely to sustain a MAIS 2+ thorax injury and had longer ICU stays. Osteopenic individuals were more likely to sustain upper extremity injuries and fractures, and were less likely to be discharged to a rehabilitation facility. Osteosarcopenic individuals were less likely to be ventilated or admitted to the ICU but tended to spend more time on the ventilator if placed on one. Conclusions: Osteosarcopenia was not associated with any injury outcomes, but sarcopenia was associated with thoracic injury and osteopenia was associated with upper extremity injury incidence. Sarcopenia was only associated with ICU length of stay, while osteopenia was only associated with discharge destination. Osteosarcopenia was associated with likelihood of being ventilated, being admitted to the ICU, and with increased length of ventilation.

Introduction: Sleeve gastrectomy (SG) is an increasingly used and effective treatment for obesity; however, the rapid weight loss associated with SG adversely affects bone metabolism predisposing patients to skeletal fragility. Bisphosphonate medications have been evaluated for safety and efficacy in combating bone loss in patients with osteoporosis, but their use in SG-induced bone loss is limited. The goal of this study is to investigate how a one-time infusion of zoledronic acid compares to placebo, in its ability to combat SG-associated bone loss., Methods and Analysis: This research protocol is a 9-month, pilot randomized controlled trial (RCT) involving 30 adult SG patients randomised to receive an infusion of either 5 mg of zoledronic acid or placebo, 6 weeks following surgery. To be included participants must be <350 lbs/158.8 kg, free of bone-impacting pathologies or medications, and must have adequate serum calcium and vitamin D levels at baseline. The primary outcome is change in areal bone mineral density (aBMD) at the total hip. Secondary outcomes include change in aBMD of the femoral neck, and lumbar spine, and change in volumetric BMD at the lumbar spine. The primary aim will be tested using a linear mixed model fit with total hip aBMD at 9 months as the outcome. Treatment, participant sex and menopausal status will be considered in analysis. Groups will be compared using contrast statements at 9 months, with change over 9 months being the primary comparison., Ethics and Dissemination: This study was approved by the Institutional Review Board of the University of Nebraska Medical Center (IRB820-19). Written consent will be obtained from participants at enrolment by trained staff. Careful and thorough explanation are used in obtainment of consent and voluntariness is emphasised throughout the trial. The findings of this study will be presented locally, nationally, and published in peer-reviewed journals. Additional details will be reported on ClinicalTrials.gov., Trial Registration Number: NCT04279392., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of this study was to explore the efficacy of 150 mg once monthly oral risedronate use in the prevention of sleeve gastrectomy (SG) associated bone loss. Twenty-four SG patients (56 ± 7 years, 83% female, 21% black) were randomized to risedronate or placebo for 6 months, with an optional 12-month assessment. Outcome measures included 6 (n = 21) and 12 (n = 14) month change in dual energy x-ray absorptiometry-acquired regional areal bone mineral density (aBMD). Six-month treatment effect estimates [mean (95% CI)] revealed significant between group aBMD differences at the femoral neck [risedronate: +0.013 g/cm 2 (-0.021, 0.046) vs. placebo: -0.041 g/cm 2 (-0.067, -0.015)] and lumbar spine [risedronate: +0.028 g/cm 2 (-0.006, 0.063) vs. placebo: -0.029 g/cm 2 (-0.054, -0.004)]; both p ≤ 0.02. When followed postoperatively to 12 months, differential aBMD treatment effects were observed at the total hip [risedronate: -0.035 g/cm 2 (-0.061, -0.009) vs. placebo: -0.072 g/cm 2 (-0.091, -0.052)] and lumbar spine [risedronate: +0.012 g/cm 2 (-0.038, 0.063) vs. placebo: -0.052 g/cm 2 (-0.087, -0.017)]; both p < 0.05. Preliminary treatment effect estimates signal 6 months of risedronate use may be efficacious in reducing aBMD loss at the axial skeleton post-SG, with benefit largely maintained throughout the 1-year postoperative period. Confirmatory data from an adequately powered trial are needed., (© 2021 World Obesity Federation.)

Background: Dietary recommendations may underestimate the protein older adults need for optimal bone health. This study sought to determine associations of protein intake with bone mineral density (BMD) and fracture among community-dwelling White and Black older adults., Method: Protein as a percentage of total energy intake (TEI) was assessed with a Food Frequency Questionnaire in 2160 older adults (73.5 ± 2.8 years; 51.5% women; 35.8% Black) in the Health, Aging, and Body Composition prospective cohort. Hip, femoral neck, and whole body BMD was assessed by dual-energy x-ray absorptiometry at baseline and 4 years, and lumbar trabecular, cortical, and integral BMD was assessed by computed tomography at baseline and 5 years. Fragility fractures over 5 years were adjudicated from self-report data collected every 6 months. Associations with tertiles of protein intake were assessed using analysis of covariance for BMD and multivariate Cox regression for fracture, adjusting for confounders., Results: Participants in the upper protein tertile (≥15% TEI) had 1.8%-6.0% higher mean hip and lumbar spine BMD compared to the lower protein tertile (<13% TEI; p < .05). Protein intake did not affect change in BMD at any site over the follow-up period. Participants in the upper protein tertile had a reduced risk of clinical vertebral fracture over 5 years of follow-up (hazard ratio: 0.36 [95% confidence interval: 0.14, 0.97] vs lower protein tertile, p = .04)., Conclusions: Older adults with higher protein intake (≥15% TEI) had higher BMD at the hip, whole body, and lumbar spine, and a lower risk of vertebral fracture., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pseudomonas aeruginosa is an opportunistic human pathogen implicated in both acute and chronic diseases, which resists antibiotic treatment, in part by forming physical and chemical barriers such as biofilms. Here, we explore the use of confocal Raman imaging to characterize the three-dimensional (3D) spatial distribution of alkyl quinolones (AQs) in P. aeruginosa biofilms by reconstructing depth profiles from hyperspectral Raman data. AQs are important to quorum sensing (QS), virulence, and other actions of P. aeruginosa. Three-dimensional distributions of three different AQs (PQS, HQNO, and HHQ) were observed to have a significant depth, suggesting 3D anisotropic shapes-sheet-like rectangular solids for HQNO and extended cylinders for PQS. Similar to observations from 2D imaging studies, spectral features characteristic of AQs (HQNO or PQS) and the amide I vibration from peptide-containing species were found to correlate with the PQS cylinders typically located at the tips of the HQNO rectangular solids. In the QS-deficient mutant lasIrhlI, a small globular component was observed, whose highly localized nature and similarity in size to a P. aeruginosa cell suggest that the feature arises from HHQ localized in the vicinity of the cell from which it was secreted. The difference in the shapes and sizes of the aggregates of the three AQs in wild-type and mutant P. aeruginosa is likely related to the difference in the cellular response to growth conditions, environmental stress, metabolic levels, or other structural and biochemical variations inside biofilms. This study provides a new route to characterizing the 3D structure of biofilms and shows the potential of confocal Raman imaging to elucidate the nature of heterogeneous biofilms in all three spatial dimensions. These capabilities should be applicable as a tool in studies of infectious diseases.

Background: Achievement of 5-10% weight loss (WL) among older adults living with obesity considerably improves prognosis of health-related outcomes; however, concomitant declines in bone mineral density (BMD) limit overall benefit by increasing fracture risk. Declines in mechanical loading contribute to WL-associated BMD loss, with pilot data signaling the addition of external weight replacement (via weighted vest use) during intentional WL mitigates bone loss at weight bearing sites to a similar degree as resistance exercise training (RT). Definitive data in support of weighted vest use as a potential strategy to mitigate WL-associated bone loss in this population are needed., Methods: In the Incorporating Nutrition, Vests, Education, and Strength Training (INVEST) in Bone Health trial (NCT04076618), 192 older adults (60-85 years) who are overweight (BMI ≥ 27 kg/m 2 ) with at least one obesity-related risk factor or obese (BMI = 30-40 kg/m 2 ) will be randomly assigned to participate in one of three 12-month intervention groups: WL alone, WL + weighted vest use (WL + VEST), or WL + RT. The primary aim is to determine the effects of WL + VEST compared to WL alone and WL + RT on indicators of bone health and subsequent fracture risk., Discussion: Determining effective, translatable strategies that minimize bone loss during intentional WL among older adults holds public health potential. The INVEST in Bone Health trial offers an innovative approach for increasing mechanical stress during intentional WL in the absence of RT. If successful, findings from this study will provide evidence in support of a scalable solution to minimize bone loss during intentional WL among older adults with obesity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There are many hydrated surface niches that are neither static nor continuously flowing that are colonized by microbes such as bacteria. Such periodic hydrodynamic regimes are distinct from aquatic systems where microbial dissemination is reasonably predicted by assuming continuous flow or static systems where motile microbes largely control their own fate. Here we show how non-motile bacteria exhibit rapid, dispersive bursts of movement over surfaces using transient confluent hydration from the environment, which we term "surface hydrodispersion" where cells traverse thousands of cell lengths within minutes. The fraction of the population disseminated by surface hydrodispersion is small-on order of 1 cell per million. Thus, surface hydrodispersion can promote isolated distribution of single cells, which is unlike other characterized active and passive surface motilities. We describe this translocation using a continuous time random walk modeling approach and find in computational simulations that transient fluid accumulation, dilution, and gravitational pull are the contributing factors. Surface hydrodispersion, consistent with advection, is unlike simple colony expansion as it dramatically alters spatial relationships, shown here with Staphylococcus aureus , which becomes increasingly virulent when isolated from Corynebacterium striatum Surface hydrodispersion of non-motile bacteria exploiting transient fluid availability and gravity is a mechanism that can result in sporadic and sudden shifts in microbial community behavior. To better understand how this movement can impact biogeography on the millimeter scale, this work describes a system for study of primary factors behind this movement as well as a stochastic model describing this dispersal. Importance: Understanding the dynamics within microbiome communities is a challenge. Knowledge of phylogeny and spatial arrangement has led to increased understanding of numerous polymicrobial communities yet, these snapshots do not convey the dynamics of populations over time. The actual biogeography of any microbiome controls the potential interactions, governing any possible antagonistic or synergistic behavior. Accordingly, a shift in biogeography can enable new behavior. Little is known about the movement mechanisms of "non-motile" microbes. Here we characterize a universal means of movement we term hydrodispersion where non-motile bacteria are transported thousands of cell lengths in minutes. We show that only a small fraction of the population is translocated by hydrodispersion and describe this movement further using a random-walk mathematical model approach in silico We demonstrate the importance of hydrodispersion by showing that Staphylococcus aureus can separate from a coculture inoculation with Corynebacterium striatum thus permitting transition to a more virulent state., (Copyright © 2021 American Society for Microbiology.)

Astronauts exposed to microgravity for extended time are susceptible to trunk muscle atrophy, which may compromise strength and function on mission and after return. This study investigates changes in trunk skeletal muscle size and composition using computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) among 16 crewmembers (1 female, 15 male) on 4-6 month missions. Muscle cross-sectional area and muscle attenuation were measured using abdominal CT scans at pre-flight, post-flight return, 1 year post-flight, and 2-4 years post-flight. Longitudinal muscle changes were analyzed using mixed models. In six crewmembers, CT and DXA data were used to calculate subject height-normalized skeletal muscle indices. Changes in these indices were analyzed using paired t-tests and compared by imaging modality using Pearson correlations. Trunk muscle area decreased at post-flight return (- 4.7 ± 1.1%, p < 0.001) and recovered to pre-flight values at 1-4 years post-flight. Muscle attenuation changes were not significant. Skeletal muscle index from CT decreased (- 5.2 ± 1.0%, p = 0.004) while appendicular skeletal muscle index from DXA did not change significantly. In summary, trunk muscle atrophies with long-duration microgravity exposure but recovers to pre-flight values within 1-4 years. The CT measures highlight size decreases not detected with DXA, emphasizing the importance of advanced imaging modalities in assessing muscle health with spaceflight.

Background: Muscle metrics derived from computed tomography (CT) are associated with adverse health events in older persons, but obtaining these metrics using current methods is not practical for large datasets. We developed a fully automated method for muscle measurement on CT images. This study aimed to determine the relationship between muscle measurements on CT with survival in a large multicenter trial of older adults., Method: The relationship between baseline paraspinous skeletal muscle area (SMA) and skeletal muscle density (SMD) and survival over 6 years was determined in 6,803 men and 4,558 women (baseline age: 60-69 years) in the National Lung Screening Trial (NLST). The automated machine learning pipeline selected appropriate CT series, chose a single image at T12, and segmented left paraspinous muscle, recording cross-sectional area and density. Associations between SMA and SMD with all-cause mortality were determined using sex-stratified Cox proportional hazards models, adjusted for age, race, height, weight, pack-years of smoking, and presence of diabetes, chronic lung disease, cardiovascular disease, and cancer at enrollment., Results: After a mean 6.44 ± 1.06 years of follow-up, 635 (9.33%) men and 265 (5.81%) women died. In men, higher SMA and SMD were associated with a lower risk of all-cause mortality, in fully adjusted models. A one-unit standard deviation increase was associated with a hazard ratio (HR) = 0.85 (95% confidence interval [CI] = 0.79, 0.91; p < .001) for SMA and HR = 0.91 (95% CI = 0.84, 0.98; p = .012) for SMD. In women, the associations did not reach significance., Conclusion: Higher paraspinous SMA and SMD, automatically derived from CT exams, were associated with better survival in a large multicenter cohort of community-dwelling older men., (Published by Oxford University Press on behalf of The Gerontological Society of America 2020.)

Objective: Obesity has important implications for motor vehicle safety due to altered crash injury responses from increased mass and improper seatbelt placement. Abdominal seatbelt signs (ASBS) above the anterior superior iliac spine (ASIS) in motor vehicle crashes (MVCs) often correlate with abdominopelvic trauma. We investigated the relationship of body mass index (BMI), lap belt placement, and the incidence of abdominopelvic injury using computed tomography (CT) evaluation for subcutaneous ASBS mark and its location relative to the ASIS., Methods: A retrospective analysis of 235 Crash Injury Research and Engineering Network (CIREN) cases and their associated abdominal injuries was conducted. CT Scans were analyzed to visualize fat stranding. 150 positive ASBS were found and their ASBS mark location was classified as superior, on, or inferior to the ASIS., Results: Obese occupants had a higher incidence rate of belt placement superior to the ASIS, and occupants with normal BMI had a higher incidence of proper belt placement (p < 0.05). Trends of interest developed, notably that non-obese occupants with superior belt placement had increased incidence of internal abdominopelvic organ injury compared to those with proper belt placement (Normal BMI: 53.3% superior vs 39.4% On-ASIS, Overweight: 47.8% superior vs 34.7% On-ASIS)., Conclusions: Utilizing CT scans to confirm ASBS and lap belt placement relative to the ASIS, superior belt placement above the ASIS was associated with elevated BMI and a trend of increasing incidence of internal abdominopelvic organ injury.

Objective: The objective of this study was to develop injury risk curves as a function of change in vehicle velocity for occupants in far-side lateral motor vehicle crashes (MVCs) by AIS level, body region, and specific AIS codes that commonly occur in this crash mode., Methods: The National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) years 2000-2015 database was queried, resulting in 4,495 non-weighted far-side crashes. For each case, occupant age, sex, and the following metadata were collected: vehicle model year, vehicle body type, lateral delta-v, normalized PDOF, multiple impacts, belt use, seat position, object contacted, striking vehicle body type, maximum crush extent and side airbag deployment. Multivariable logistic regression was used to develop risk curves for AIS 2+ through 5+ injuries, AIS 2+ injuries by body region (head, thorax, lower extremity), and for each of the 10 most frequent far-side AIS 2+ injuries. Significant covariates were determined by backwards elimination (p < 0.05). The full dataset and a subsampled dataset of only cases with side airbag deployment were used to develop risk curves., Results: For AIS 2+ through 5+ injury, greater delta-V was associated with greater injury risk (OR's: 2.48-3.66 per 11.9 kph increase) and belt use was associated with lower risk (OR's: 0.04-0.36 compared to unbelted). Multiple impacts were significant predictors of increased AIS 3+, 4+ and 5+ injury risk (OR's: 2.56, 2.27 and 2.83 compared to single impact). For AIS 2+ body region injuries, lateral delta-V and maximum CDC extent were positively associated with increased head, thorax and lower extremity injury risk while belt use was associated with lower risk. Increased lateral delta-v, unbelted status, and greater maximum CDC extent frequently increased injury risk for the most common far-side injuries. Side airbag deployment was not a significant covariate for the injury risk models., Conclusions: The resulting risk models expand upon previous literature gaps to provide a more comprehensive view of contributors to injury risk for occupants in far-side MVCs. This study yields risk curves based on the latest available NASS-CDS data.

Mounting evidence implicates bariatric surgery as a cause of increased skeletal fragility and fracture risk. Bisphosphonate therapy reduces osteoporotic fracture risk and may be effective in minimizing bone loss associated with bariatric surgery. The main objective of this pilot randomized controlled trial (RCT; Clinical Trial No. NCT03411902) was to determine the feasibility of recruiting, treating, and following 24 older patients who had undergone sleeve gastrectomy in a 6 month RCT examining the efficacy of 150-mg once-monthly risedronate (versus placebo) in the prevention of surgical weight-loss-associated bone loss. Feasibility was defined as: (i) >30% recruitment yield, (ii) >80% retention, (iii) >80% pills taken, (iv) <20% adverse events (AEs), and (v) >80% participant satisfaction. Study recruitment occurred over 17 months. Seventy participants were referred, with 24 randomized (34% yield) to risedronate ( n = 11) or placebo ( n = 13). Average age was 56 ± 7 years, 83% were female (63% postmenopausal), and 21% were black. The risedronate group had a higher baseline BMI than the placebo group (48.1 ± 7.2 versus 41.9 ± 3.8 kg/m 2 ). The 10-year fracture risk was low (6.0% major osteoporotic fracture, 0.4% hip fracture); however, three individuals (12.5%, all risedronate group) were osteopenic at baseline. Twenty-one participants returned for 6-month follow-up testing (88% retention) with all ( n = 3) loss to follow-up occurring in the risedronate group. Average number of pills taken among completers was 5.9 ± 0.4 and 6.0 ± 0.0 in the risedronate and placebo groups, respectively ( p = 0.21), with active participants taking >80% of allotted pills. Five AEs (3.7% AE rate) were reported; one definitely related, four not related, and none serious. All participants reported high satisfaction with participation in the study. Use of bisphosphonates as a novel therapeutic to preserve bone density in patients who had undergone a sleeve gastrectomy appears feasible and well-tolerated. Knowledge gained from this pilot RCT will be used to inform the design of an appropriately powered trial., Clinical Trial Registration: http://clinicaltrials.gov/show/NCT03411902. Weight Loss With Risedronate for Bone Health. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

The goals of this study are to compare the lumbar spine response variance between the hybrid III, test device for human occupant restraint (THOR), and global human body models consortium simplified 50th percentile (GHBMC M50-OS) finite element models and evaluate the sensitivity of lumbar spine injury metrics to multidirectional acceleration pulses for spaceflight landing conditions. The hybrid III, THOR, and GHBMC models were positioned in a baseline posture within a generic seat with side guards and a five-point restraint system. Thirteen boundary conditions, which were categorized as loading condition variables and environmental variables, were included in the parametric study using a Latin hypercube design of experiments. Each of the three models underwent 455 simulations for a total of 1365 simulations. The hybrid III and THOR models exhibited similar lumbar compression forces. The average lumbar compression force was 45% higher for hybrid III (2.2 ± 1.5 kN) and 51% higher for THOR (2.0 ± 1.6 kN) compared to GHBMC (1.3 ± 0.9 kN). Compared to hybrid III, THOR sustained an average 64% higher lumbar flexion moment and an average 436% higher lumbar extension moment. The GHBMC model sustained much lower bending moments compared to hybrid III and THOR. Regressions revealed that lumbar spine responses were more sensitive to loading condition variables than environmental variables across all models. This study quantified the intermodel lumbar spine response variations and sensitivity between hybrid III, THOR, and GHBMC. Results improve the understanding of lumbar spine response in spaceflight landings., (Copyright © 2020 by ASME.)

A two to three period analytical chemistry experiment has been developed which allows second year students to explore chemical color tests used to detect adulterated pharmaceuticals. Students prepare several paper analytical devices (PADs) to generate positive and negative controls antibiotics, along with cutting agents such as starch and chalk. These PADs are used to identify the active ingredients and excipients in mystery tablets prepared by their classmates. In the second part of the lab, the students select an individual color test and design an experiment to quantify their mystery pill's active pharmaceutical ingredient (API). Nearly all of the student groups were able to successfully identify adulterants present in their mystery tablets. The quantification of the mystery tablets was also successful with all but one group calculating the correct concentration within 6%. In a postlab assessment, the students identified their largest gains in their ability to analyze data and other information, skill in science writing, and learning of laboratory techniques., Competing Interests: The authors declare the following competing financial interest(s): One author, M.L., holds a patent (US 009354181B2) on the paper analytical devices (PADs) used in this study. Licensing negotiations for this patent with a U.S. company are underway. The U.S. patent will not prevent others from manufacturing or selling PADs., (Copyright © 2020 American Chemical Society and Division of Chemical Education, Inc.)