Health-related quality of life in breast cancer patients treated with CDK4/6 inhibitors: a systematic review.

BACKGROUND: Evaluation of health-related quality of life (HR-QoL) among cancer patients has gained an increasing importance and is now a key determinant of anticancer treatments' value. HR-QoL has been assessed in trials testing cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in breast cancer (BC), using various questionnaires at different timepoints. HR-QoL reports from BC patients treated with CDK4/6i in the real-world setting are also available. METHODS: We systematically reviewed the literature, searching for full-length articles, and selected conference abstracts reporting data on HR-QoL in BC patients at any stage and of any molecular subtype treated with abemaciclib, palbociclib or ribociclib. RESULTS: A total of 533 full-length articles and 143 abstracts were retrieved. After screening for eligibility, 38 records were included (31 clinical trials; 7 real-world reports). Assessment methods were heterogeneous across studies in terms of questionnaires, evaluation timepoints and endpoints. Overall, adding CDK4/6i to endocrine therapy did not worsen patients' HR-QoL, with a positive trend towards pain improvement. Gastrointestinal scores (diarrhea, nausea and appetite loss) statistically favored the control arm among metastatic BC patients receiving abemaciclib, whereas they were superimposable in the early setting. The combination of palbociclib and endocrine therapy showed similar HR-QoL outcomes compared with endocrine therapy alone, but determined better scores compared with chemotherapy. HR-QoL was specifically assessed in premenopausal patients treated with ribociclib, showing similar scores compared with postmenopausal patients. CONCLUSIONS: Despite methodological heterogeneity does not allow a proper comparison, HR-QoL was generally maintained with CDK4/6i. However, differences between abemaciclib, palbociclib and ribociclib exist and mainly rely on the distinct safety profiles of the compounds. These differences should be acknowledged and taken into account in the clinical practice.

Evaluation of Error-State Kalman Filter Method for Estimating Human Lower-Limb Kinematics during Various Walking Gaits.

Inertial measurement units (IMUs) offer an attractive way to study human lower-limb kinematics without traditional laboratory constraints. We present an error-state Kalman filter method to estimate 3D joint angles, joint angle ranges of motion, stride length, and step width using data from an array of seven body-worn IMUs. Importantly, this paper contributes a novel joint axis measurement correction that reduces joint angle drift errors without assumptions of strict hinge-like joint behaviors of the hip and knee. We evaluate the method compared to two optical motion capture methods on twenty human subjects performing six different types of walking gait consisting of forward walking (at three speeds), backward walking, and lateral walking (left and right). For all gaits, RMS differences in joint angle estimates generally remain below 5 degrees for all three ankle joint angles and for flexion/extension and abduction/adduction of the hips and knees when compared to estimates from reflective markers on the IMUs. Additionally, mean RMS differences in estimated stride length and step width remain below 0.13 m for all gait types, except stride length during slow walking. This study confirms the method's potential for non-laboratory based gait analysis, motivating further evaluation with IMU-only measurements and pathological gaits.

Virulomic Analysis of Multidrug-Resistant Klebsiella pneumoniae Isolates and Experimental Virulence Model Using Danio rerio (Zebrafish).

This study evaluates a possible correlation between multidrug-resistant Klebsiella pneumoniae strains and virulence markers in a Danio rerio (zebrafish) model. Whole-genome sequencing (WGS) was performed on 46 strains from three Brazilian hospitals. All of the isolates were colistin-resistant and harbored blaKPC-2. Ten different sequence types (STs) were found; 63% belonged to CC258, 22% to ST340, and 11% to ST16. The virulence factors most frequently found were type 3 fimbriae, siderophores, capsule regulators, and RND efflux-pumps. Six strains were selected for a time-kill experiment in zebrafish embryos: infection by ST16 was associated with a significantly higher mortality rate when compared to non-ST16 strains (52% vs. 29%, p = 0.002). Among the STs, the distribution of virulence factors did not differ significantly except for ST23, which harbored a greater variety of factors than other STs but was not related to a higher mortality rate in zebrafish. Although several virulence factors are described in K. pneumoniae, our study found ST16 to be the only significant predictor of a virulent phenotype in an animal model. Further research is needed to fully understand the correlation between virulence and sequence types.

Testicular alterations in cryptorchid/orchiopexic rats chronically exposed to acrylamide or di-butyl-phthalate.

Exposure of Sprague-Dawley (SD) rats to acrylamide (AA) or di-butyl-phthalate (DBP) from the 12th gestational day to the 16th postnatal week (PNW) has been shown to reduce the effectiveness of orchiopexy in recovering the testicular alterations associated with experimental cryptorchidism established at weaning. Herein, we provide information about the long-term effects of AA or DBP on the testes of cryptorchid/orchiopexic rats. Male offspring exposed in utero to 10 mg/kg/day AA or 500 mg/kg/day DBP underwent bilateral surgical cryptorchidism at the 3rd PNW and orchiopexy at the 6th week, with continuous exposure to the chemicals through diet until the 58th week. Regardless of the test chemical, there were severe qualitative/quantitative alterations in the seminiferous tubules and increased numbers of Leydig cells. There was an increase and decrease in the number of tubules with c-Kit- and placental alkaline phosphatase-labeled germ cells, respectively, as compared to those in the control group, suggesting an imbalance between apoptosis and cell proliferation processes. The histological scores of the testicular lesions at the end of this one-year study were higher than those in the previous 16-week study, indicating that exposure of rats to the toxicants AA or DBP enhanced the testicular alterations induced by the chemicals beginning at the intra-uterine life, and impaired the effectiveness of orchiopexy in restoring the testes to normal morphology. Although the present experimental protocol does not completely replicate the natural human undescended testes, our findings may contribute to understanding the alterations occurring in cryptorchid/orchiopexic testes potentially exposed to exogenous chemicals for extended periods.

GLP-1 and GIP receptor agonists in the treatment of Parkinson's disease: Translational systematic review and meta-analysis protocol of clinical and preclinical studies.

BACKGROUND: Parkinson's disease (PD) is a progressive multifactorial neurodegenerative condition. Epidemiological studies have shown that patients with type 2 diabetes mellitus (T2DM2) are at increased risk for developing PD, indicating a possible insulin-modulating role in this latter condition. We hypothesized that drugs similar to glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), used in the treatment of T2DM2, may play a role in PD. OBJECTIVES: The purpose of this study is to systematically review and meta-analyze data of preclinical and clinical studies evaluating the efficacy and safety of GLP-1 and GIP drugs in the treatment of PD. METHODS: Two reviewers will independently evaluate the studies available in the Ovid Medline, Ovid Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cinahl, and Lilacs databases. Preclinical rodent or non-human primate studies and randomized controlled human clinical trials will be included, without language or publication period restrictions. Outcomes of interest in preclinical studies will be primarily locomotor improvements and adverse effects in animal models of PD. For clinical trials, we will evaluate clinical improvements rated by the Movement Disorders Society Unified Parkinson's Disease Rating Scale-parts I, II, III, and IV, and adverse effects. The risk of bias of preclinical studies will be assessed by the SYRCLE tool and CAMARADES checklist and the clinical studies by the Cochrane tool; the certainty of the evidence will be rated by GRADE. DISCUSSION AND CONCLUSION: There is an urge for new PD treatments that may slow the progression of the disease rather than just restoring dopamine levels. This study will comprehensively review and update the state of the art of what is known about incretin hormones and PD and highlight the strengths and limitations of translating preclinical data to the clinic whenever possible. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020223435.

Automated Loss-of-Balance Event Identification in Older Adults at Risk of Falls during Real-World Walking Using Wearable Inertial Measurement Units.

Loss-of-balance (LOB) events, such as trips and slips, are frequent among community-dwelling older adults and are an indicator of increased fall risk. In a preliminary study, eight community-dwelling older adults with a history of falls were asked to perform everyday tasks in the real world while donning a set of three inertial measurement sensors (IMUs) and report LOB events via a voice-recording device. Over 290 h of real-world kinematic data were collected and used to build and evaluate classification models to detect the occurrence of LOB events. Spatiotemporal gait metrics were calculated, and time stamps for when LOB events occurred were identified. Using these data and machine learning approaches, we built classifiers to detect LOB events. Through a leave-one-participant-out validation scheme, performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPR). The best model achieved an AUROC ≥0.87 for every held-out participant and an AUPR 4-20 times the incidence rate of LOB events. Such models could be used to filter large datasets prior to manual classification by a trained healthcare provider. In this context, the models filtered out at least 65.7% of the data, while detecting ≥87.0% of events on average. Based on the demonstrated discriminative ability to separate LOBs and normal walking segments, such models could be applied retrospectively to track the occurrence of LOBs over an extended period of time.

Genetic factors involved in fosfomycin resistance of multidrug-resistant Acinetobacter baumannii.

The treatment of infections caused by A. baumannii is a challenge and fosfomycin has been used as a combination therapy. Moreover, data regarding the fosfomycin resistance mechanism is scarce. The goals of this study were to evaluate fosfomycin susceptibility in polyclonal multi-resistant A. baumannii isolates and characterize the fosfomycin resistance. We analyzed 32 A. baumannii isolates from a Brazilian bacterial collection, followed by their minimum inhibitory concentration (MIC), and whole-genome sequence to detect fosfomycin resistance genes. The isolates showed a fosfomycin MIC ranging from 32 to ≥256 mg/L. All isolates were negative for fosA and fosB genes, and four isolates carried the fosX gene. Two different metabolic pathways that form peptidoglycan precursors were identified. Mutations were observed in the adenylate cyclase gene. All A. baumannii isolates studied showed Val132Ala substitutions in MurA. The analysis showed different ways that may lead to the intrinsic fosfomycin-resistance of A. baumannii, such as alterations on the glycerol-3-phosphate transporter system caused by adenylate cyclase mutations; and a possible connection of cell wall recycling by different metabolic pathways.

Carbapenem-resistant Serratia marcescens bloodstream infection in hematopoietic stem cell transplantation patients: Will it be the next challenge?

Surveillance programs have been reporting decreasing rates of carbapenem-sensitivity in Serratia marcescens, leading to a concern regarding the few remaining therapeutic options to treat these multidrug-resistant (MDR) organisms. Here, we describe a case series of 11 stem cell hematopoietic transplantation patients infected (N = 6) or colonized (N = 5) by carbapenem-resistant S marcescens (CrSm) from 2010 to 2013. The comorbidities found were acute renal insufficiency (3/11), neutropenia (7/11), and mucositis (8/11), and the mortality rate was 64%. KPC was the most prevalent carbapenemase detected (8/11) and tigecycline and gentamicin were the antimicrobials used as treatment.

Error-state Kalman filter for lower-limb kinematic estimation: Evaluation on a 3-body model.

Human lower-limb kinematic measurements are critical for many applications including gait analysis, enhancing athletic performance, reducing or monitoring injury risk, augmenting warfighter performance, and monitoring elderly fall risk, among others. We present a new method to estimate lower-limb kinematics using an error-state Kalman filter that utilizes an array of body-worn inertial measurement units (IMUs) and four kinematic constraints. We evaluate the method on a simplified 3-body model of the lower limbs (pelvis and two legs) during walking using data from simulation and experiment. Evaluation on this 3-body model permits direct evaluation of the ErKF method without several confounding error sources from human subjects (e.g., soft tissue artefacts and determination of anatomical frames). RMS differences for the three estimated hip joint angles all remain below 0.2 degrees compared to simulation and 1.4 degrees compared to experimental optical motion capture (MOCAP). RMS differences for stride length and step width remain within 1% and 4%, respectively compared to simulation and 7% and 5%, respectively compared to experiment (MOCAP). The results are particularly important because they foretell future success in advancing this approach to more complex models for human movement. In particular, our future work aims to extend this approach to a 7-body model of the human lower limbs composed of the pelvis, thighs, shanks, and feet.

Time response of rat testicular alterations induced by cryptorchidism and orchiopexy.

Cryptorchidism is one of the main risk factors for infertility and testicular cancer. Orchiopexy surgery corrects cryptorchidism effects. Different models of cryptorchidism developed in the rat include surgery. We assessed testicular alterations in rats submitted to surgical cryptorchidism and examined their potential for reversibility at different time points in order to verify time dependency effect(s) on the recovery of the undescended testes. Cryptorchidism was induced in 3-week-old rats. Animals were euthanized 3, 6 or 11 weeks after surgery to evaluate the morphological progression of cryptorchidism-induced germinative epithelial alterations. Other groups underwent orchiopexy 3, 5 or 9 weeks after surgical cryptorchidism, before or after puberty. Animals were euthanized 3 or 8 weeks after orchiopexy. Controls underwent sham surgery at the same time points as the surgical groups. Cryptorchid testes showed decreased weight, germinative epithelial degeneration, apoptosis and vacuolation, corresponding to impairment of spermatogenesis and of Sertoli cells. Some tubules has a Sertoli cell-only pattern and atrophy. The intensity of damage was related to the duration of cryptorchidism. After orchiopexy, spermatogenesis completely recovered only when testicular relocation occurred before puberty and the interval for recovery was extended. These results indicate that age, sexual maturity and extension of germ cell damage were relevant for producing germ cell restoration and normal spermatogenesis. We provide original observations on the time dependency of testicular alterations induced by cryptorchidism and their restoration using morphologic, morphometric and immunohistochemical approaches. It may be useful to study germ cell impairment, progression and recovery in different experimental settings, including exposure to exogenous chemicals.

Human walking in the real world: Interactions between terrain type, gait parameters, and energy expenditure.

Humans often traverse real-world environments with a variety of surface irregularities and inconsistencies, which can disrupt steady gait and require additional effort. Such effects have, however, scarcely been demonstrated quantitatively, because few laboratory biomechanical measures apply outdoors. Walking can nevertheless be quantified by other means. In particular, the foot's trajectory in space can be reconstructed from foot-mounted inertial measurement units (IMUs), to yield measures of stride and associated variabilities. But it remains unknown whether such measures are related to metabolic energy expenditure. We therefore quantified the effect of five different outdoor terrains on foot motion (from IMUs) and net metabolic rate (from oxygen consumption) in healthy adults (N = 10; walking at 1.25 m/s). Energy expenditure increased significantly (P < 0.05) in the order Sidewalk, Dirt, Gravel, Grass, and Woodchips, with Woodchips about 27% costlier than Sidewalk. Terrain type also affected measures, particularly stride variability and virtual foot clearance (swing foot's lowest height above consecutive footfalls). In combination, such measures can also roughly predict metabolic cost (adjusted R2 = 0.52, partial least squares regression), and even discriminate between terrain types (10% reclassification error). Body-worn sensors can characterize how uneven terrain affects gait, gait variability, and metabolic cost in the real world.

Detection of Real-World Trips in At-Fall Risk Community Dwelling Older Adults Using Wearable Sensors.

Background: Near-falls such as a trip, slip, stumble, or misstep involve a loss of balance (LOB) that does not result in a fall, occur more frequently than actual falls, and are associated with an increased fall risk. To date, studies have largely involved detection of simulated laboratory LOBs using wearable devices in young adults. Data on the detection of and kinematics of naturally occurring LOBs in people at high risk of falling are lacking. This may provide a new way to identify older adults at high risk for falls. We aimed to explore key body kinematics underlying real-world trips in at-fall risk community dwelling older adults wearing inertial measurement units (IMU). Methods: Five community-dwelling older adults with a history of falls who reported trips during the study period participated. They wore a voice recorder and 4 IMUs mounted on feet, lower back and wrist for two consecutive weeks to provide a record of the context and timing of LOB events. Sensor data prior to time-stamped voice recording of a trip were processed in order to visually identify unusual foot trajectories and lower back and arm orientations. Then, data of feet, lower back and wrist position and orientation were combined to create a three-dimensional animation representing the estimated body motion during the noted time segments in order to corroborate the occurrence of a trip. Events reported as a trip by the participant and identified as a trip by a researcher, blinded to voice recordings description, were included in the final analysis. Results: A total of 18 trips obtained from five participants were analyzed. Twelve trips occurred at home, three outside and for three the location was not reported. Trips were identified in the sensor data by observing (1) additional peaks to the typical foot velocity signal during swing phase; (2) increased velocity of the contralateral foot and (3) sharp changes in lower back pitch angles. Conclusions: Our approach demonstrates the feasibility of identifying and studying the mechanisms and context underlying trip-related LOBs in at-fall risk older adults during real world activities.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins.

In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 µg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.

Genetic and virulence characterization of colistin-resistant and colistin-sensitive A. baumannii clinical isolates.

Treatment of infections caused by A. baumannii is becoming a challenge due to the ability to develop multidrug-resistance, virulence, and high mortality. We described the colistin resistance and virulence genes present in sixA. baumannii clinical isolates using WGS, expression by qPCR, and virulence in the Galleria mellonella model. The colistin-resistant isolates were assigned as ST233 and the colistin-susceptible isolates as ST236 and ST407. The colistin-resistant isolates contained mutations within PmrA/PmrB, and the pmrA showed up-regulation in all of them. Only one colistin-resistant isolate indicating virulence in G. mellonella. This particular isolate belonged to a different clone, and it was the only isolate that presented non-synonymous mutations in pmrB. Colistinresistance in A. baumannii isolates seems to be caused by up-regulation of pmrA gene. Only one isolate appeared to be virulent in the G. mellonella model. This finding indicating low virulence in isolates belonging to emerging clones circulating in our hospital.

Effect of IMU Design on IMU-Derived Stride Metrics for Running.

Researchers employ foot-mounted inertial measurement units (IMUs) to estimate the three-dimensional trajectory of the feet as well as a rich array of gait parameters. However, the accuracy of those estimates depends critically on the limitations of the accelerometers and angular velocity gyros embedded in the IMU design. In this study, we reveal the effects of accelerometer range, gyro range, and sampling frequency on gait parameters (e.g., distance traveled, stride length, and stride angle) estimated using the zero-velocity update (ZUPT) method. The novelty and contribution of this work are that it: (1) quantifies these effects at mean speeds commensurate with competitive distance running (up to 6.4 m/s); (2) identifies the root causes of inaccurate foot trajectory estimates obtained from the ZUPT method; and (3) offers important engineering recommendations for selecting accurate IMUs for studying human running. The results demonstrate that the accuracy of the estimated gait parameters generally degrades with increased mean running speed and with decreased accelerometer range, gyro range, and sampling frequency. In particular, the saturation of the accelerometer and/or gyro induced during running for some IMU designs may render those designs highly inaccurate for estimating gait parameters.

Isolation and molecular characterization of spermatogonia from male Sprague-Dawley rats exposed in utero and postnatally to dibutyl phthalate or acrylamide.

The increased incidence of testicular disorders in young men and the possible influence of environmental chemicals, such as dibutyl phthalate (DBP) and acrylamide (AA), requires experimental models for identifying modes of action. Most published reproductive toxicologic studies use RNA samples from the total testis to evaluate testicular gene expression; however, analyses of isolated cell types could provide a more specific tool. Among testicular germ cells, spermatogonia are critical since they represent the onset of spermatogenesis. This study aimed, (1) to establish a technique for spermatogonia isolation; (2) to apply this isolation technique to verify possible gene expression alterations (Pou5f1, Kitlg, Mki-67, Bak1 and Spry4) in prepubertal post-natal day, (PND24) and pubertal (PND45) testes after in utero and postnatal exposure to DBP or AA. The technique was efficient for isolation of a majority of spermatogonia. In utero DBP exposure led to reduced litter body weight at birth, reduced anogenital distance of male pups on PND4, and increased frequency of male nipple retention on PND14 compared to controls. DBP-exposed relative testes weights were reduced only at PND24 compared to control but they did not differ at PND45. DBP-exposed animals showed reduced expression levels of Pou5f1 and Mki67 on PND24, and reduced expression of Pou5f1 and Spry4 on PND45. AA exposure reduced expression of Pou5f1, Mki67, and Spry4 at PND45 although not significantly. Our results suggest that DBP acts by reducing cell proliferation and impairing differentiation in prepubertal and pubertal testes.

Body-worn IMU array reveals effects of load on performance in an outdoor obstacle course.

This study introduces a new method to understand how added load affects human performance across a broad range of athletic tasks (ten obstacles) embedded in an outdoor obstacle course. The method employs an array of wearable inertial measurement units (IMUs) to wirelessly record the movements of major body segments to derive obstacle-specific metrics of performance. The effects of load are demonstrated on (N = 22) participants who each complete the obstacle course under four conditions including unloaded (twice) and with loads of 15% and 30% of their body weight (a total of 88 trials across the group of participants). The IMU-derived performance metrics reveal marked degradations in performance with increasing load across eight of the ten obstacles. Overall, this study demonstrates the significant potential in using this wearable technology to evaluate human performance across multiple tasks and, simultaneously, the adverse effects of body-borne loads on performance. The study addresses a major need of military organizations worldwide that frequently employ standardized obstacle courses to understand how added loads influence warfighter performance. Importantly, the findings and conclusions drawn from IMU data would not be possible using traditional timing metrics used to evaluate task performance.

Reconstruction of body motion during self-reported losses of balance in community-dwelling older adults.

Older adults experience slips, trips, stumbles, and other losses of balance (LOBs). LOBs are more common than falls and are closely linked to falls and fall-injuries. Data about real-world LOBs is limited, particularly information quantifying the prevalence, frequency, and intrinsic and extrinsic circumstances in which they occur. This paper describes a new method to identify and analyze LOBs through long-term recording of community-dwelling older adults. The approach uses wearable inertial measurement units (IMUs) on the feet, trunk and one wrist, together with a voice recorder for immediate, time-stamped self-reporting of the type, context and description of LOBs. Following identification of an LOB in the voice recording, concurrent IMU data is used to estimate foot paths and body motions, and to create body animations to analyze the event. In this pilot study, three older adults performed a long-term monitoring study, with four weeks recording LOBs by voice and two concurrent weeks wearing IMUs. This report presents a series of LOB cases to illustrate the proposed method, and how it can contribute to interpretation of the causes and contexts of the LOBs. The context and timing information from the voice records was critical to the process of finding and analyzing LOB events within the voluminous sensor data record, and included much greater detail, specificity, and nuance than past diary or smartphone reporting.

Estimating Stair Running Performance Using Inertial Sensors.

Stair running, both ascending and descending, is a challenging aerobic exercise that many athletes, recreational runners, and soldiers perform during training. Studying biomechanics of stair running over multiple steps has been limited by the practical challenges presented while using optical-based motion tracking systems. We propose using foot-mounted inertial measurement units (IMUs) as a solution as they enable unrestricted motion capture in any environment and without need for external references. In particular, this paper presents methods for estimating foot velocity and trajectory during stair running using foot-mounted IMUs. Computational methods leverage the stationary periods occurring during the stance phase and known stair geometry to estimate foot orientation and trajectory, ultimately used to calculate stride metrics. These calculations, applied to human participant stair running data, reveal performance trends through timing, trajectory, energy, and force stride metrics. We present the results of our analysis of experimental data collected on eleven subjects. Overall, we determine that for either ascending or descending, the stance time is the strongest predictor of speed as shown by its high correlation with stride time.

Method for Estimating Three-Dimensional Knee Rotations Using Two Inertial Measurement Units: Validation with a Coordinate Measurement Machine.

Three-dimensional rotations across the human knee serve as important markers of knee health and performance in multiple contexts including human mobility, worker safety and health, athletic performance, and warfighter performance. While knee rotations can be estimated using optical motion capture, that method is largely limited to the laboratory and small capture volumes. These limitations may be overcome by deploying wearable inertial measurement units (IMUs). The objective of this study is to present a new IMU-based method for estimating 3D knee rotations and to benchmark the accuracy of the results using an instrumented mechanical linkage. The method employs data from shank- and thigh-mounted IMUs and a vector constraint for the medial-lateral axis of the knee during periods when the knee joint functions predominantly as a hinge. The method is carefully validated using data from high precision optical encoders in a mechanism that replicates 3D knee rotations spanning (1) pure flexion/extension, (2) pure internal/external rotation, (3) pure abduction/adduction, and (4) combinations of all three rotations. Regardless of the movement type, the IMU-derived estimates of 3D knee rotations replicate the truth data with high confidence (RMS error < 4 ° and correlation coefficient r ≥ 0.94 ).