Cross-Cutting mHealth Behavior Change Techniques to Support Treatment Adherence and Self-Management of Complex Medical Conditions: Systematic Review.

Background: Mobile health (mHealth) interventions have immense potential to support disease self-management for people with complex medical conditions following treatment regimens that involve taking medicine and other self-management activities. However, there is no consensus on what discrete behavior change techniques (BCTs) should be used in an effective adherence and self-management-promoting mHealth solution for any chronic illness. Reviewing the extant literature to identify effective, cross-cutting BCTs in mHealth interventions for adherence and self-management promotion could help accelerate the development, evaluation, and dissemination of behavior change interventions with potential generalizability across complex medical conditions. Objective: This study aimed to identify cross-cutting, mHealth-based BCTs to incorporate into effective mHealth adherence and self-management interventions for people with complex medical conditions, by systematically reviewing the literature across chronic medical conditions with similar adherence and self-management demands. Methods: A registered systematic review was conducted to identify published evaluations of mHealth adherence and self-management interventions for chronic medical conditions with complex adherence and self-management demands. The methodological characteristics and BCTs in each study were extracted using a standard data collection form. Results: A total of 122 studies were reviewed; the majority involved people with type 2 diabetes (28/122, 23%), asthma (27/122, 22%), and type 1 diabetes (19/122, 16%). mHealth interventions rated as having a positive outcome on adherence and self-management used more BCTs (mean 4.95, SD 2.56) than interventions with no impact on outcomes (mean 3.57, SD 1.95) or those that used >1 outcome measure or analytic approach (mean 3.90, SD 1.93; P=.02). The following BCTs were associated with positive outcomes: self-monitoring outcomes of behavior (39/59, 66%), feedback on outcomes of behavior (34/59, 58%), self-monitoring of behavior (34/59, 58%), feedback on behavior (29/59, 49%), credible source (24/59, 41%), and goal setting (behavior; 14/59, 24%). In adult-only samples, prompts and cues were associated with positive outcomes (34/45, 76%). In adolescent and young adult samples, information about health consequences (1/4, 25%), problem-solving (1/4, 25%), and material reward (behavior; 2/4, 50%) were associated with positive outcomes. In interventions explicitly targeting medicine taking, prompts and cues (25/33, 76%) and credible source (13/33, 39%) were associated with positive outcomes. In interventions focused on self-management and other adherence targets, instruction on how to perform the behavior (8/26, 31%), goal setting (behavior; 8/26, 31%), and action planning (5/26, 19%) were associated with positive outcomes. Conclusions: To support adherence and self-management in people with complex medical conditions, mHealth tools should purposefully incorporate effective and developmentally appropriate BCTs. A cross-cutting approach to BCT selection could accelerate the development of much-needed mHealth interventions for target populations, although mHealth intervention developers should continue to consider the unique needs of the target population when designing these tools.

The effects of plantarflexor weakness and reduced tendon stiffness with aging on gait stability.

Falls among older adults are a costly public health concern. Such falls can be precipitated by balance disturbances, after which a recovery strategy requiring rapid, high force outputs is necessary. Sarcopenia among older adults likely diminishes their ability to produce the forces necessary to arrest gait instability. Age-related changes to tendon stiffness may also delay muscle stretch and afferent feedback and decrease force transmission, worsening fall outcomes. However, the association between muscle strength, tendon stiffness, and gait instability is not well established. Given the ankle's proximity to the onset of many walking balance disturbances, we examined the relation between both plantarflexor strength and Achilles tendon stiffness with walking-related instability during perturbed gait in older and younger adults-the latter quantified herein using margins of stability and whole-body angular momentum including the application of treadmill-induced slip perturbations. Older and younger adults did not differ in plantarflexor strength, but Achilles tendon stiffness was lower in older adults. Among older adults, plantarflexor weakness associated with greater whole-body angular momentum following treadmill-induced slip perturbations. Weaker older adults also appeared to walk and recover from treadmill-induced slip perturbations with more caution. This study highlights the role of plantarflexor strength and Achilles tendon stiffness in regulating lateral gait stability in older adults, which may be targets for training protocols seeking to minimize fall risk and injury severity.

A Data-Driven Approach to Estimate Human Center of Mass State During Perturbed Locomotion Using Simulated Wearable Sensors.

Center of mass (COM) state, specifically in a local reference frame (i.e., relative to center of pressure), is an important variable for controlling and quantifying bipedal locomotion. However, this metric is not easily attainable in real time during human locomotion experiments. This information could be valuable when controlling wearable robotic exoskeletons, specifically for stability augmentation where knowledge of COM state could enable step placement planners similar to bipedal robots. Here, we explored the ability of simulated wearable sensor-driven models to rapidly estimate COM state during steady state and perturbed walking, spanning delayed estimates (i.e., estimating past state) to anticipated estimates (i.e., estimating future state). We used various simulated inertial measurement unit (IMU) sensor configurations typically found on lower limb exoskeletons and a temporal convolutional network (TCN) model throughout this analysis. We found comparable COM estimation capabilities across hip, knee, and ankle exoskeleton sensor configurations, where device type did not significantly influence error. We also found that anticipating COM state during perturbations induced a significant increase in error proportional to anticipation time. Delaying COM state estimates significantly increased accuracy for velocity estimates but not position estimates. All tested conditions resulted in models with R2 > 0.85, with a majority resulting in R2 > 0.95, emphasizing the viability of this approach. Broadly, this preliminary work using simulated IMUs supports the efficacy of wearable sensor-driven deep learning approaches to provide real-time COM state estimates for lower limb exoskeleton control or other wearable sensor-based applications, such as mobile data collection or use in real-time biofeedback.

Habitually wearing high heels may improve user walking economy in any footwear.

The habitual use of high-heeled footwear may structurally remodel user leg muscle tendons, thereby altering their functional capabilities. High heels set users' ankles in relatively plantarflexed positions, causing calf muscle tendons to operate at relatively short lengths. Habitually operating muscle tendons at relatively short lengths induces structural remodeling that theoretically affects muscle metabolism. Because structural changes occur within the body, the user's locomotor metabolism may change in any footwear condition (e.g., conventional shoes, barefoot). Here, we studied the influence of habitual high-heel use on users' leg muscle-tendon structure and metabolism during walking in flat-soled footwear. We tested eight participants before and after 14 wk of agreeing to wear high heels as their daily shoes. Overall, participants who wore high heels >1,500 steps per day, experienced a 9% decrease in their net metabolic power during walking in flat-soled footwear (d = 1.66, P ≤ 0.049), whereas participants who took <1,000 daily steps in high heels did not (d = 0.44; P = 0.524). Across participants, for every 1,000 daily steps in high heels, net metabolic power during walking in flat-soled footwear decreased 5.3% (r = -0.73; P = 0.040). Metabolic findings were partially explained (r2 = 0.43; P = 0.478) by trending shorter medial gastrocnemius fascicle lengths (d = 0.500, P = 0.327) and increased Achilles tendon stiffness (d = 2.889, P = 0.088). The high-heel intervention did not alter user walking stride kinematics in flat-soled footwear (d ≤ 0.567, P ≥ 0.387). While our limited dataset is unable to establish the mechanisms underlying the high-heel-induced walking economy improvement, it appears that prescribing specific footwear use can be implemented to alter user muscle-tendon properties and augment their function in any shoes.NEW & NOTEWORTHY Habitually wearing high-heeled footwear structurally remodels leg muscle tendons and improves user walking economy, regardless of worn attire.

An emotional journey: caregiver experiences with gastrostomy tube decision-making for children with cystic fibrosis.

BACKGROUND: Nutritional challenges are common in early CF care and stressful for caregivers of children with CF (cwCF) to navigate. Gastrostomy tube (G-tube) placement can improve weight gain, however the decision to proceed with placement is personalized and preference-sensitive. Little is known about the experiences of caregivers of cwCF and the G-tube decision-making process. OBJECTIVES: The present study used a qualitative approach to explore the perceptions and experiences of caregivers of cwCF with G-tube introductions and recommendations, as well as factors influencing G-tube decision-making. METHODS: Caregivers of cwCF aged ≤ 10 years completed audio-taped, semi-structured interviews describing their experiences with G-tube placement discussions. Interviews were transcribed and two independent researchers coded the transcripts and conducted content and thematic analysis using an inductive approach. RESULTS: Participants included 43 caregivers, 84 % were mothers (36/43). CwCF had a mean age of 4 years (SD=2.6), 84 % were White (36/43), and 60 % reported weights below <50th percentile (26/43). All caregivers knew about G-tubes, 44 % (19/43) were recommended a G-tube and 35 % (15/43) had a G-tube placed. Major findings included descriptions of the stages of G-tube decision-making from a heads up, to the game plan, to making a first difficult decision and finally living with the decision to pursue G-tube placement. CONCLUSION: G-tube decision-making is an emotional and personalized journey for caregivers of cwCF. Efforts to explore the values and priorities of caregivers is imperative to supporting families making difficult decisions in CF care.

Continuous glucose monitoring and advanced glycation endproducts for prediction of clinical outcomes and development of cystic fibrosis-related diabetes in adults with CF.

Introductions: Cystic fibrosis-related diabetes (CFRD) is associated with pulmonary decline, compromised nutritional status, and earlier mortality. Onset is often insidious, so screening for early detection of glycemic abnormalities is important. Continuous glucose monitoring (CGM) has been validated in people with CF and has been shown to detect early glycemic variability otherwise missed on 2-hour oral glucose tolerance testing (OGTT). We previously reported that CGM measures of hyperglycemia and glycemic variability are superior to hemoglobin A1c (HbA1c) in distinguishing those with and without CFRD. However, little is known about the long-term predictive value of CGM measures of glycemia for both the development of CFRD and their effect on key clinical outcomes such as weight maintenance and pulmonary function. In addition, there have been no studies investigating advanced glycation endproducts (AGE) assessed by skin autofluorescence in people with CF. Methods: In this prospective observational study, CGM and HbA1c were measured at 2 to 3 time points 3 months apart in 77 adults with CF. Participants who did not have CFRD at the time of enrollment underwent OGTT at the baseline visit, and all participants had AGE readings at baseline. Follow up data including anthropometric measures, pulmonary function and CFRD status were collected by review of medical records 1- and 2-years after the baseline visits. We applied multivariable linear regression models correlating glycemic measures to change in key clinical outcomes (weight, BMI, FEV1) accounting for age, gender and elexacaftor/tezacaftor/ivacaftor (ETI) use. We also conducted logistic regression analyses comparing baseline glycemic data to development of CFRD during the 2-year follow up period. Results: Of the 77 participants, 25 had pre-existing CFRD at the time of enrollment, and six participants were diagnosed with CFRD by the OGTT performed at the baseline visit. When adjusting for age, gender, and ETI use, multiple CGM measures correlated with weight and BMI decline after one year but not after two years. CGM and HbA1c at baseline did not predict decline in FEV1 (p>0.05 for all). In the 46 participants without a diagnosis of CFRD at baseline, two participants were diagnosed with CFRD over the following two years, but CGM measures at baseline did not predict progression to CFRD. Baseline AGE values were higher in individuals with CFRD and correlated with multiple measures of dysglycemia (HbA1c, AG, SD, CV, TIR, % time >140, >180, >250) as well as weight. AGE values also correlated with FEV1 decline at year 1 and weight decline at year 1 and year 2. Conclusions: Several key CGM measures of hyperglycemia and glycemic variability were predictive of future decline in weight and BMI over one year in this population of adults with CF with and without CFRD. None of the baseline glycemic variables predicted progression to CFRD over 2 years. To our knowledge, this is the first report correlating AGE levels with key clinical and glycemic measures in CF. Limitations of these analyses include the small number of participants who developed CFRD (n=2) during the follow up period and the initiation of ETI by many participants, affecting their trajectory in weight and pulmonary function. These results provide additional data supporting the potential role for CGM in identifying clinically significant dysglycemia in CF. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD and to understand the implications of AGE measures in this patient population.

Safety and Pharmacokinetics Following Oral or Intravenous Lefamulin in Adults With Cystic Fibrosis.

PURPOSE: Methicillin-resistant Staphylococcus aureus infections are increasing in prevalence in patients with cystic fibrosis (CF) and are associated with worsening lung function and increased mortality. Lefamulin is a pleuromutilin antimicrobial approved to treat community-acquired bacterial pneumonia based on potent in vitro activity and clinical efficacy. This Phase I, open-label, randomized crossover study assessed the safety and pharmacokinetic profile of oral and intravenous (IV) lefamulin in adults with CF. METHODS: The study comprised 2 dosing periods in which adults with CF (N = 13) received a single dose of lefamulin via a 150-mg IV infusion or 600-mg immediate-release orally administered tablet, separated by a 4- to 7-day washout period. Pharmacokinetic and safety parameters were assessed after lefamulin treatment. FINDINGS: Single doses of lefamulin administered via oral tablet or IV infusion resulted in comparable drug exposure, and sputum analysis suggested rapid penetration of lefamulin into the lung. Comparison of the present results with those obtained from prior single-dose studies of healthy volunteers indicate no meaningful difference in the pharmacokinetic properties of lefamulin in patients with CF. Treatment-emergent adverse events were consistent with previous reports, and the majority were mild in severity. IMPLICATIONS: These results show similar lefamulin pharmacokinetic and safety profiles between patients with CF and healthy volunteers receiving the same oral and IV doses, suggesting no need for lefamulin dose adjustment in patients with CF and indicating the potential of lefamulin as therapy for lung infections in patients with CF. CLINICALTRIALS: gov identifier: NCT05225805.

Attenuation of muscle spindle firing with artificially increased series compliance during stretch of relaxed muscle.

Muscle spindles relay vital mechanosensory information for movement and posture, but muscle spindle feedback is coupled to skeletal motion by a compliant tendon. Little is known about the effects of tendon compliance on muscle spindle feedback during movement, and the complex firing of muscle spindles makes these effects difficult to predict. Our goal was to investigate changes in muscle spindle firing using added series elastic elements (SEEs) to mimic a more compliant tendon, and to characterize the accompanying changes in firing with respect to muscle-tendon unit (MTU) and muscle fascicle displacements (recorded via sonomicrometry). Sinusoidal, ramp-and-hold and triangular stretches were analysed to examine potential changes in muscle spindle instantaneous firing rates (IFRs) in locomotor- and perturbation-like stretches as well as serial history dependence. Added SEEs effectively reduced overall MTU stiffness and generally reduced muscle spindle firing rates, but the effect differed across stretch types. During sinusoidal stretches, peak and mean firing rates were not reduced and IFR was best-correlated with fascicle velocity. During ramp stretches, SEEs reduced the initial burst, dynamic and static responses of the spindle. Notably, IFR was negatively related to fascicle displacement during the hold phase. During triangular stretches, SEEs reduced the mean IFR during the first and second stretches, affecting the serial history dependence of mean IFR. Overall, these results demonstrate that tendon compliance may attenuate muscle spindle feedback during movement, but these changes cannot be fully explained by reduced muscle fascicle length or velocity, or MTU force.

Randomized Trial of the Insulin-Only iLet Bionic Pancreas for the Treatment of Cystic Fibrosis- Related Diabetes.

OBJECTIVE: Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis and adds significant morbidity and treatment burden. We evaluated the safety and efficacy of automated insulin delivery with the iLet bionic pancreas (BP) in adults with CFRD in a single-center, open-label, random-order, crossover trial. RESEARCH DESIGN AND METHODS: Twenty participants with CFRD were assigned in random order to 14 days each on the BP or their usual care (UC). No restrictions were placed on diet or activity. The primary outcome was the percent time sensor-measured glucose was in target range 70-180 mg/dL (time in range [TIR]) on days 3-14 of each arm, and key secondary outcomes included mean continuous glucose monitoring (CGM) glucose and the percent time sensor-measured glucose was in hypoglycemic range <54 mg/dL. RESULTS: TIR was significantly higher in the BP arm than the UC arm (75 ± 11% vs. 62 ± 22%, P = 0.001). Mean CGM glucose was lower in the BP arm than in the UC arm (150 ± 19 vs. 171 ± 45 mg/dL, P = 0.007). There was no significant difference in percent time with sensor-measured glucose <54 mg/dL (0.27% vs. 0.36%, P = 1.0), although self-reported symptomatic hypoglycemia episodes were higher during the BP arm than the UC arm (0.7 vs. 0.4 median episodes per day, P = 0.01). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either arm. CONCLUSIONS: Adults with CFRD had improved glucose control without an increase in CGM-measured hypoglycemia with the BP compared with their UC, suggesting that this may be an important therapeutic option for this patient population.

Reduced Achilles tendon stiffness in aging persists at matched activations and associates with higher metabolic cost of walking.

The mechanisms responsible for increased walking metabolic cost among older adults are poorly understood. We recently proposed a theoretical premise by which age-related reductions in Achilles tendon stiffness (k AT ) can disrupt the neuromechanics of calf muscle behavior and contribute to faster rates of oxygen consumption during walking. The purpose of this study was to objectively evaluate this premise. We quantified k AT at a range of matched activations prescribed using electromyographic biofeedback and walking metabolic cost in a group of 15 younger (age: 23±4 yrs) and 15 older adults (age: 72±5 yrs). Older adults averaged 44% less k AT than younger adults at matched triceps surae activations (p=0.046). This effect appeared to arise not only from altered tendon length-tension relations with age, but also from differences in the operating region of those length-tension relations between younger and older adults. Older adults also walked with a 17% higher net metabolic power than younger adults (p=0.017). In addition, we discovered empirical evidence that lesser k AT exacts a metabolic penalty and was positively correlated with higher net metabolic power during walking (r=-0.365, p=0.048). These results pave the way for interventions focused on restoring ankle muscle-tendon unit structural stiffness to improve walking energetics in aging.

Predictive Control of Peak Achilles Tendon Force in a Simulated System of the Human Ankle Joint with a Parallel Artificial Actuator During Hopping.

Latest advances in wearable exoskeletons for the human lower extremity predominantly focus on minimising metabolic cost of walking. However, there currently is no robotic exoskeleton that gains control on the mechanics of biological tissues such as biological muscles or series-elastic tendons. Achieving robotic control of biological tissue mechanics would enable prevention of musculoskeletal injuries or the personalization of rehabilitation treatments following injury with levels of precisions not attained before. In this paper, we introduce a new framework that uses nonlinear model predictive control (NMPC) for the closed-loop control of peak tendon force in a simulated system of the human ankle joint with parallel exoskeletal actuation. We propose a computationally efficient NMPC's inner model consisting of explicit, closed-form equations of muscle-tendon dynamics along with those of the ankle joint with parallel actuation. The proposed formulation is tested and verified on movement data collected during dynamic ankle dorsiflexion/plantarflexion rotations executed on a dynamometer as well as during walking and running on a treadmill. The framework designed using the NMPC controller showed a promising performance in keeping the Achilles tendon force under a predefined threshold. Results indicated that our proposed model was generalizable to different muscles and gaits and suitable for real-time applications due to its low computational time.

Clinician perspectives and practices related to sexual and reproductive care provision for males with cystic fibrosis.

BACKGROUND: Males with cystic fibrosis (MwCF) have unique sexual and reproductive health (SRH) concerns. This study investigates multidisciplinary CF clinician perspectives related to SRH for MwCF in the current era of CF care. METHODS: We surveyed multidisciplinary clinicians exploring attitudes, practices, and preferences toward male CF SRH care. We compared responses across groups by population served (pediatric vs. adult vs. both pediatric and adult MwCF) using chi square/Fisher's exact tests. RESULTS: A total of 297 clinicians completed the survey (41 % pediatric, 36 % adult, 23 % both; 27 % physicians, 24 % social workers, 11 % nurses, 41 % other). Nearly all (98 %) believed the CF team had a role in SRH care with 75 % believing they should be primarily responsible. Pediatric clinicians were less likely to deem SRH topics important and less likely to report annual discussions compared to adult colleagues (all p<0.05). Pediatric clinicians reported less comfort in their SRH knowledge than adult colleagues (p<0.001) and in their ability to provide SRH care (p<0.05). Common barriers endorsed by respondents included lack of SRH knowledge (75 %) and presence of family/partners in exam room (64 %). A majority rated SRH screening tools (91 %), partnerships with SRH specialists (90 %), clinician training (83 %), and management algorithms (83 %) as potential facilitators. CONCLUSION: Multidisciplinary CF clinicians perceive SRH for MwCF as important but report suboptimal SRH discussions. Pediatric clinicians report significantly less comfort and skill in discussing and managing male SRH. Identified barriers and facilitators should be used to improve SRH care for MwCF.

Simulations suggest walking with reduced propulsive force would not mitigate the energetic consequences of lower tendon stiffness.

Aging elicits numerous effects that impact both musculoskeletal structure and walking function. Tendon stiffness (kT) and push-off propulsive force (FP) both impact the metabolic cost of walking and are diminished by age, yet their interaction has not been studied. We combined experimental and computational approaches to investigate whether age-related changes in function (adopting smaller FP) may be adopted to mitigate the metabolic consequences arising from changes in structure (reduced kT). We recruited 12 young adults and asked them to walk on a force-sensing treadmill while prompting them to change FP (±20% & ±40% of typical) using targeted biofeedback. In models driven by experimental data from each of those conditions, we altered the kT of personalized musculoskeletal models across a physiological range (2-8% strain) and simulated individual-muscle metabolic costs for each kT and FP combination. We found that kT and FP independently affect walking metabolic cost, increasing with higher kT or as participants deviated from their typical FP. Our results show no evidence for an interaction between kT and FP in younger adults walking at fixed speeds. We also reveal complex individual muscle responses to the kT and FP landscape. For example, although total metabolic cost increased by 5% on average with combined reductions in kT and FP, the triceps surae muscles experienced a 7% local cost reduction on average. Our simulations suggest that reducing FP during walking would not mitigate the metabolic consequences of lower kT. Wearable devices and rehabilitative strategies can focus on either kT or FP to reduce age-related increases in walking metabolic cost.

American Society of Biomechanics Journal of Biomechanics Award 2021: Exploring the Functional Boundaries and Metabolic Consequences of Triceps Surae Force-Length Relations during Walking.

The relationship between individual muscle dynamics and whole-body metabolic cost is not well established. Here we use biofeedback to modulate triceps surae (TS) activity during walking to test the following hypotheses based on basic principles of muscle physiology: (1) increased TS activity would increase metabolic cost via shorter muscle fascicle lengths and thus reduced force capacity and (2) decreased TS activity would decrease metabolic cost via longer muscle fascicle lengths and thus increased force capacity. 23 young adults walked on an instrumented treadmill at 1.25 m/s using electromyographic (EMG) biofeedback to match targets corresponding to ±20 and ±40% TS activity during push-off (late stance). B-mode ultrasound imaged the medial gastrocnemius (MG). Participants increased net metabolic power up to 85% and 21% when targeting increased and decreased TS activity, respectively (p < 0.001). At the instant of peak gastrocnemius force, MG fascicle length was 7% shorter (p < 0.001) and gastrocnemius force was 6% larger (p < 0.001) when targeting + 40% TS activity. Fascicle length was 3% shorter (p = 0.004) and force was 7% lower (p = 0.010) when targeting -40% TS activity; participants were unable to achieve decreased activation targets. MG fascicle length and activity mediated 11.7% (p = 0.036) and 57.2% (p = 0.006) of the changes in net metabolic power, respectively. MG force did not mediate changes in net metabolic power (p = 0.948). These findings suggest that changes in the functional operating length of muscle, induced here by volitional changes in TS activity, mediated changes in the metabolic cost of walking, relatively independently of force. Thus, shifts to shorter fascicle lengths (e.g., aging) may mediate activity-induced increases in metabolic cost.

Partners in research: The success with therapies research consortium and the CF community unite to improve self-management.

BACKGROUND: The daily treatment regimen for an individual with cystic fibrosis (CF) can take more than 2 h to complete, and chronic treatment adherence rates are low. Developing partnerships between CF clinical researchers and the CF community is essential in developing acceptable, feasible, and effective strategies to improve self-management and adherence. METHODS: The Success with Therapies Research Consortium (STRC) was formed as a multi-center US collaborative to conduct rigorous research studies of adherence to CF treatments. A multidisciplinary team of researchers from 15 sites, collaborating with members of the CF community, is charged with developing, implementing, and disseminating real-world, patient-centered interventions for people living with CF. RESULTS: Since 2014, the STRC has conducted 8 studies. The CF community, people with CF (pwCF), and caregivers have come to serve in multiple valuable capacities on the STRC, including as members of the Steering Committee and Co-Principal Investigators. Additionally, while people with CF are irreplaceable participants in STRC studies, their influence, and that of their families and healthcare professionals, extends beyond the traditional research participant role. CONCLUSIONS: Engaging broadly with the CF community is the optimal model for developing interventions to support those living with CF in sustaining daily care. Input and direct involvement from people with CF, their families, and their caregivers has enabled the STRC to advance its mission through innovative clinical research approaches.

The influence of induced gait asymmetry on joint reaction forces.

Chronic injury- or disease-induced joint impairments result in asymmetric gait deviations that may precipitate changes in joint loading associated with pain and osteoarthritis. Understanding the impact of gait deviations on joint reaction forces (JRFs) is challenging because of concurrent neurological and/or anatomical changes and because measuring JRFs requires medically invasive instrumented implants. Instead, we investigated the impact of joint motion limitations and induced asymmetry on JRFs by simulating data recorded as 8 unimpaired participants walked with bracing to unilaterally and bilaterally restrict ankle, knee, and simultaneous ankle + knee motion. Personalized models, calculated kinematics, and ground reaction forces (GRFs) were input into a computed muscle control tool to determine lower limb JRFs and simulated muscle activations guided by electromyography-driven timing constraints. Unilateral knee restriction increased GRF peak and loading rate ipsilaterally but peak values decreased contralaterally when compared to walking without joint restriction. GRF peak and loading rate increased with bilateral restriction compared to the contralateral limb of unilaterally restricted conditions. Despite changes in GRFs, JRFs were relatively unchanged due to reduced muscle forces during loading response. Thus, while joint restriction results in increased limb loading, reductions in muscle forces counteract changes in limb loading such that JRFs were relatively unchanged.

Attenuation of muscle spindle firing with artificially increased series compliance during stretch of relaxed muscle.

Muscle spindles relay vital mechanosensory information for movement and posture, but muscle spindle feedback is coupled to skeletal motion by a compliant tendon. Little is known about the effects of tendon compliance on muscle spindle feedback during movement, and the complex firing of muscle spindles make these effects difficult to predict. Our goal was to investigate changes in muscle spindle firing using added series elastic elements (SEEs) to mimic a more compliant tendon, and to characterize the accompanying changes in firing with respect to muscle-tendon unit (MTU) and muscle fascicle displacements (recorded via sonomicrometry). Sinusoidal, ramp-hold-release, and triangular stretches were analyzed to examine potential changes in muscle spindle instantaneous firing rates (IFRs) in locomotor- and perturbation-like stretches as well as history dependence. Added SEEs effectively reduced overall MTU stiffness and generally reduced muscle spindle firing rates, but the effect differed across stretch types. During sinusoidal stretches, peak firing rates were reduced and IFR was strongly correlated with fascicle velocity. During ramp stretches, SEEs reduced the dynamic and static responses of the spindle during lengthening but had no effect on initial bursts at the onset of stretch. Notably, IFR was negatively related to fascicle displacement during the hold phase. During triangular stretches, SEEs reduced the mean IFR during the first and second stretches, affecting the history dependence of mean IFR. Overall, these results demonstrate that tendon compliance may attenuate muscle spindle feedback during movement, but these changes cannot be fully explained by reduced muscle fascicle length and velocity.

Perturbing the muscle work loop paradigm to unravel the neuromechanics of unsteady locomotion.

Muscle function during movement is more than a simple, linear transformation of neural activity into force. The classic work loop technique has pioneered our understanding of muscle, but typically only characterizes function during unperturbed movement cycles, such as those experienced during steady walking, running, swimming and flying. Yet perturbations away from steady movement often place greater demands on muscle structure and function and offer a unique window into muscle's broader capacity. Recently, studies in diverse organisms from cockroaches to humans have started to grapple with muscle function in unsteady (perturbed, transient and fluctuating) conditions, but the vast range of possible parameters and the challenge of connecting in vitro to in vivo experiments are daunting. Here, we review and organize these studies into two broad approaches that extend the classic work loop paradigm. First, in the top-down approach, researchers record length and activation patterns of natural locomotion under perturbed conditions, replay these conditions in isolated muscle work loop experiments to reveal the mechanism by which muscle mediates a change in body dynamics and, finally, generalize across conditions and scale. Second, in the bottom-up approach, researchers start with an isolated muscle work loop and then add structural complexity, simulated loads and neural feedback to ultimately emulate the muscle's neuromechanical context during perturbed movement. In isolation, each of these approaches has several limitations, but new models and experimental methods coupled with the formal language of control theory give several avenues for synthesizing an understanding of muscle function under unsteady conditions.

The influence of elastic ankle exoskeletons on lower limb mechanical energetics during unexpected perturbations.

Passive elastic ankle exoskeletons have been used to augment locomotor performance during walking, running and hopping. In this study, we aimed to determine how these passive devices influence lower limb joint and whole-body mechanical energetics to maintain stable upright hopping during rapid, unexpected perturbations. We recorded lower limb kinematics and kinetics while participants hopped with exoskeleton assistance (0, 76 and 91 Nm rad-1) on elevated platforms (15 and 20 cm) which were rapidly removed at an unknown time. Given that springs cannot generate nor dissipate energy, we hypothesized that passive ankle exoskeletons would reduce stability during an unexpected perturbation. Our results demonstrate that passive exoskeletons lead to a brief period of instability during unexpected perturbations - characterized by increased hop height. However, users rapidly stabilize via a distal-to-proximal redistribution of joint work such that the knee performs an increased energy dissipation role and stability is regained within one hop cycle. Together, these results demonstrate that despite the inability of elastic exoskeletons to directly dissipate mechanical energy, humans can still effectively dissipate the additional energy of a perturbation, regain stability and recover from a rapid unexpected vertical perturbation to maintain upright hopping.