Duloxetine and Cognitive Behavioral Therapy with Phone-based Support for the Treatment of Chronic Musculoskeletal Pain: Study Protocol of the PRECICE Randomized Control Trial.

Background: Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT. Methods: Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of 3 treatment arms: (1) combination treatment (duloxetine + web-based self-guided CBT) with phone-based motivational interviewing (MI), (2) combination treatment without phone-based MI and (3) duloxetine monotherapy. Participants will be in the study for 24 weeks and will be assessed at baseline, week 13, and week 25. The primary outcome is the Brief Pain Inventory (BPI)-Global Pain Severity score, which combines BPI pain severity and BPI pain interference. Secondary measures include between-group comparisons in mean BPI pain severity and BPI pain interference scores. Data collection and outcome assessment will be blinded to treatment group assignment. Discussion: This randomized controlled trial (RCT) will determine if combination treatment with duloxetine and web-based CBT is superior to duloxetine monotherapy for the management of CMP. Furthermore, this RCT will determine the effectiveness of phone-based motivational interviewing in promoting the continued practice of pain coping skills; thereby, enhancing treatment outcomes. Trial Registration: NCT04395001. Registered in ClinicalTrials.gov on May 15, 2020.

Inferring Stochastic Rates from Heterogeneous Snapshots of Particle Positions.

Many imaging techniques for biological systems-like fixation of cells coupled with fluorescence microscopy-provide sharp spatial resolution in reporting locations of individuals at a single moment in time but also destroy the dynamics they intend to capture. These snapshot observations contain no information about individual trajectories, but still encode information about movement and demographic dynamics, especially when combined with a well-motivated biophysical model. The relationship between spatially evolving populations and single-moment representations of their collective locations is well-established with partial differential equations (PDEs) and their inverse problems. However, experimental data is commonly a set of locations whose number is insufficient to approximate a continuous-in-space PDE solution. Here, motivated by popular subcellular imaging data of gene expression, we embrace the stochastic nature of the data and investigate the mathematical foundations of parametrically inferring demographic rates from snapshots of particles undergoing birth, diffusion, and death in a nuclear or cellular domain. Toward inference, we rigorously derive a connection between individual particle paths and their presentation as a Poisson spatial process. Using this framework, we investigate the properties of the resulting inverse problem and study factors that affect quality of inference. One pervasive feature of this experimental regime is the presence of cell-to-cell heterogeneity. Rather than being a hindrance, we show that cell-to-cell geometric heterogeneity can increase the quality of inference on dynamics for certain parameter regimes. Altogether, the results serve as a basis for more detailed investigations of subcellular spatial patterns of RNA molecules and other stochastically evolving populations that can only be observed for single instants in their time evolution.

Experimental accumulation and depuration kinetics and natural occurrence of microcystin-LR in basil (Ocimum basilicum L.).

Microcystin-LR (MC-LR) is a hepatotoxic metabolite that naturally occurs during some cyanobacterial blooms in eutrophic waterbodies, and irrigation of edible plants with MC-LR-contaminated water causes bioaccumulation of the toxin. However, sufficient information about accumulation and depuration mechanics in hydroculture-grown herb plants is still lacking. This work aimed at 1) investigating bioaccumulation and depuration of MC-LR in basil, 2) verifying the possible MC-LR detoxification mechanisms in the plant, and 3) detecting the natural occurrence of MC-LR in basil (n = 50) collected from the Belgian market. Basil plants grown in a hydroculture were exposed to MC-LR (5, 20, and 50 µg L-1) spiked in a Hoagland solution for seven days. MC-LR depuration was also studied by transferring the plants to a non-contaminated Hoagland solution after exposure to MC-LR for another seven days. MC-LR concentrations in Hoagland solution, basil leaves, and roots were quantified using a validated UHPLC-MS/MS method. In addition, ELISA and LC-HRMS (only basil leaves) were used for confirmation. The results showed an increase in the accumulated levels of MC-LR at higher exposure doses, with higher MC-LR levels in roots than in leaves for all the treatment conditions. For MC-LR depuration, significant reductions were observed in all the treatment conditions for roots only. No MC-LR conjugates, potentially related to metabolism, were detected by LC-HRMS. Finally, MC-LR was detected in one store-bought basil sample, representing the first occurrence of cyanotoxins in an edible crop from Belgium.

Intrinsic statistical separation of subpopulations in heterogeneous collective motion via dimensionality reduction.

Collective motion of locally interacting agents is found ubiquitously throughout nature. The inability to probe individuals has driven longstanding interest in the development of methods for inferring the underlying interactions. In the context of heterogeneous collectives, where the population consists of individuals driven by different interactions, existing approaches require some knowledge about the heterogeneities or underlying interactions. Here, we investigate the feasibility of identifying the identities in a heterogeneous collective without such prior knowledge. We numerically explore the behavior of a heterogeneous Vicsek model and find sufficiently long trajectories intrinsically cluster in a principal component analysis-based dimensionally reduced model-agnostic description of the data. We identify how heterogeneities in each parameter in the model (interaction radius, noise, population proportions) dictate this clustering. Finally, we show the generality of this phenomenon by finding similar behavior in a heterogeneous D'Orsogna model. Altogether, our results establish and quantify the intrinsic model-agnostic statistical disentanglement of identities in heterogeneous collectives.

Working memory prioritisation effects in tactile immediate serial recall.

There is a growing body of evidence that higher-value information can be prioritised for both visual and auditory working memory. The present study examines whether valuable items can similarly be prioritised for the tactile domain. Employing an immediate serial recall procedure (ISR), participants reconstructed a 6-item tactile sequence by moving their fingers in the order of original stimulation. Participants were informed either that one serial position was worth notionally more points (prioritisation condition) or that all items were of equal value (control condition). For Experiment 1 (N = 48), significant boosts in correct recall were evident when serial positions 4 or 5 were more valuable (i.e., prioritisation effects). Experiment 2 (N = 24) demonstrated that the prioritisation effect persisted with concurrent articulation, suggesting that task performance was not a function of verbal recoding and rehearsal of the tactile information. Importantly, a significant recall cost for low-value (non-prioritised) items within the sequence was evident for both experiments. Taken together, these findings demonstrate that (1) prioritisation effects transfer to the tactile domain and (2) finite attentional resources can be deliberately and strategically redistributed to specific items within a sequence, dependent upon the prevailing task demands.

Screening and Referral for Behavioral Health Symptoms in Collegiate Athletes.

OBJECTIVE: We aim to investigate the prevalence of behavioral health symptoms in collegiate athletes and the frequency of referrals prompted by a preparticipation behavioral health screener. DESIGN: Athletes completed a screening battery to detect behavioral health symptoms and sports psychology clinicians designed criteria for intervention based on the severity of symptoms reported. Data from the screener was retrospectively de-identified and analyzed. SETTING: National Collegiate Athletic Association Division-I university. PARTICIPANTS: All athletes on active rosters were required to complete the screener as a component of the preparticipation examination. INTERVENTIONS: Sports psychology clinicians created a protocol for intervention based on the number and severity of symptoms reported on the screener. MAIN OUTCOME MEASURES: Communication with athletes and referrals made to behavioral health services. RESULTS: Of the 1126 surveys completed, 39% had behavioral health symptoms necessitating behavioral health referral. Twelve percent required a safety check-in, given the severity of their symptoms. Seven percent of the respondents were newly established with behavioral health services. CONCLUSIONS: Symptoms of behavioral health disorders are common among athletes and yet, for a myriad of reasons, many choose to forgo treatment. By implementing a behavioral health screening battery, the prevalence of behavioral health symptoms among athletes at our institution was elucidated and many athletes were newly established with behavioral health services. The tiered intervention protocol in this study allowed for appropriate assessment and triage of high-risk individuals, while simultaneously providing lower-risk individuals with appropriate resources. Surveillance for behavioral health symptoms among college athletes using a screening battery with a tiered intervention protocol can ensure at-risk athletes are identified, contacted, and referred to behavioral health services, potentially improving their athletic performance and overall well-being, while averting poor outcomes.

Microcystin profiles in European noble crayfish Astacus astacus and water in Lake Steinsfjorden, Norway.

Lake Steinsfjorden, an important noble crayfish (Astacus astacus) habitat, is often affected by blooms of Planktothrix spp. that produce microcystins (MCs). A poor correlation between MCs by ELISA in the water and in crayfish tissue in a study in 2015 prompted further investigation by LC-HRMS. LC-HRMS analyses of filters from water samples and on selected crayfish tissue extracts from the 2015 study revealed the presence of known and previously unreported MCs. Crayfish samples from May and June 2015 were dominated by MCs from the Planktothrix bloom, whereas in September novel MCs that appeared to be metabolites of MC-LR were dominant, even though neither these nor MC-LR were detected in the water in 2015. A water sample from October 2016 also showed MCs typical of Planktothrix (i.e., [d-Asp3]- and [d-Asp3,Dhb7]MC-RR and -LR), but low levels of MC-RR and MC-LR were detected in the lake water for the first time. In late summer and autumn, the MC profiles of crayfish were dominated by the homonorvaline (Hnv) variant MC-LHnv, a putative metabolite of MC-LR. Taken together, ELISA, LC-HRMS and previous PCR analyses showed that although Planktothrix was part of the crayfish diet, it was not the sole source of MCs in the crayfish. Possibly, crayfish in Lake Steinsfjorden may be ingesting MCs from benthic cyanobacteria or from contaminated prey. Therefore, information on the cyanobacterial or MC content in the water column cannot safely be used to make predictions about MC concentrations in the crayfish in Lake Steinsfjorden. Interestingly, the results also show that targeted LC-MS analysis of the crayfish would at times have underestimated their MC content by nearly an order of magnitude, even if all previously reported MC variants had been included in the analysis.

CARE4Kids Study: Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: Study Rationale and Protocol.

Treatment of youth concussion during the acute phase continues to evolve, and this has led to the emergence of guidelines to direct care. While symptoms after concussion typically resolve in 14-28 days, a portion (∼20%) of adolescents endorse persistent post-concussive symptoms (PPCS) beyond normal resolution. This report outlines a study implemented in response to the National Institute of Neurological Diseases and Stroke call for the development and initial clinical validation of objective biological measures to predict risk of PPCS in adolescents. We describe our plans for recruitment of a Development cohort of 11- to 17-year-old youth with concussion, and collection of autonomic, neurocognitive, biofluid, and imaging biomarkers. The most promising of these measures will then be validated in a separate Validation cohort of youth with concussion, and a final, clinically useful algorithm will be developed and disseminated. Upon completion of this study, we will have generated a battery of measures predictive of high risk for PPCS, which will allow for identification and testing of interventions to prevent PPCS in the most high-risk youth.

3-Epimers of Caribbean ciguatoxins in fish and algae.

Ciguatera poisoning (CP) is endemic to several subtropical and tropical regions and is caused by the consumption of fish contaminated with ciguatoxins (CTXs). The recent discovery of Caribbean CTXs (C-CTXs) in Gambierdiscus spp. isolated from the Caribbean resulted in the identification of a precursor analogue, C-CTX5, that is reduced into C-CTX1. C-CTX5 has two reducible sites, a ketone at C-3 and hemiketal at C-56. Chemical reductions of C-CTX5 into C-CTX3/4 resulted in two peaks in the LC-HRMS chromatograms with a ratio that differed markedly from that observed in fish extracts and the reduction of C-CTX1 isolated from fish. Reduction of C-CTX5 should have produced four diastereoisomers of C-CTX3/4, prompting a more detailed study of the reduction products. LC-HRMS with a slow gradient was used to separate and detect the four stereoisomers of C-CTX3/4, and to determine the distribution of these analogues in naturally contaminated fish tissues and following chemical reduction of isolated analogues. The results showed that in naturally contaminated fish tissues C-CTX1/2 is a mixture of two diastereoisomers at C-3 and that C-CTX3/4 is a mixture of two pairs of diastereoisomers at C-3 and C-56. The data suggests that there is variability in the enzymatic reduction at C-3 and C-56 of C-CTXs in reef fish, leading to variations in the ratios of the four stereoisomers. Based on these findings, a naming convention for C-CTXs is proposed which aligns with that used for Pacific CTX congeners and will aid in the identification of the structure and stereochemistry of the different CTX analogues.

Inferring stochastic rates from heterogeneous snapshots of particle positions.

Many imaging techniques for biological systems - like fixation of cells coupled with fluorescence microscopy - provide sharp spatial resolution in reporting locations of individuals at a single moment in time but also destroy the dynamics they intend to capture. These snapshot observations contain no information about individual trajectories, but still encode information about movement and demographic dynamics, especially when combined with a well-motivated biophysical model. The relationship between spatially evolving populations and single-moment representations of their collective locations is well-established with partial differential equations (PDEs) and their inverse problems. However, experimental data is commonly a set of locations whose number is insufficient to approximate a continuous-in-space PDE solution. Here, motivated by popular subcellular imaging data of gene expression, we embrace the stochastic nature of the data and investigate the mathematical foundations of parametrically inferring demographic rates from snapshots of particles undergoing birth, diffusion, and death in a nuclear or cellular domain. Toward inference, we rigorously derive a connection between individual particle paths and their presentation as a Poisson spatial process. Using this framework, we investigate the properties of the resulting inverse problem and study factors that affect quality of inference. One pervasive feature of this experimental regime is the presence of cell-to-cell heterogeneity. Rather than being a hindrance, we show that cell-to-cell geometric heterogeneity can increase the quality of inference on dynamics for certain parameter regimes. Altogether, the results serve as a basis for more detailed investigations of subcellular spatial patterns of RNA molecules and other stochastically evolving populations that can only be observed for single instants in their time evolution.

ADP release can explain spatially-dependent kinesin binding times.

The self-organization of cells relies on the profound complexity of protein-protein interactions. Challenges in directly observing these events have hindered progress toward understanding their diverse behaviors. One notable example is the interaction between molecular motors and cytoskeletal systems that combine to perform a variety of cellular functions. In this work, we leverage theory and experiments to identify and quantify the rate-limiting mechanism of the initial association between a cargo-bound kinesin motor and a microtubule track. Recent advances in optical tweezers provide binding times for several lengths of kinesin motors trapped at varying distances from a microtubule, empowering the investigation of competing models. We first explore a diffusion-limited model of binding. Through Brownian dynamics simulations and simulation-based inference, we find this simple diffusion model fails to explain the experimental binding times, but an extended model that accounts for the ADP state of the molecular motor agrees closely with the data, even under the scrutiny of penalizing for additional model complexity. We provide quantification of both kinetic rates and biophysical parameters underlying the proposed binding process. Our model suggests that most but not every motor binding event is limited by their ADP state. Lastly, we predict how these association rates can be modulated in distinct ways through variation of environmental concentrations and spatial distances.

Assessing the association between on-field heading technique and head impact kinematics in a cohort of female youth soccer players.

There is concern that exposure to soccer headers may be associated with neurological sequelae. Training proper heading technique represents a coachable intervention that may reduce head acceleration exposure. The objective was to assess relationships between heading technique and head kinematics in female youth soccer players. Fourteen players (mean age = 14.4 years) wore instrumented mouthpieces during practices and games. Headers were reviewed by three raters to assign a technique score. Mixed models and LASSO regression evaluated associations of technique with peak linear acceleration (PLA), rotational acceleration (PRA), rotational velocity (PRV), and head impact power ratio (HIP Ratio) while adjusting for session type and ball delivery. Two hundred eighty-nine headers (n = 212 standing, n = 77 jumping) were analyzed. Technique score (p = 0.043) and the technique score - session type interaction (p = 0.004) were associated with PRA of standing headers, whereby each 10-unit increase in technique score was associated with an 8.6% decrease in PRA during games but a 5.1% increase in PRA during practices. Technique was not significantly associated with any other kinematic metrics; however, peak kinematics tended to decrease as technique score increased. LASSO regression identified back extension and shoulder/hip alignment as important predictors of peak kinematics. Additional research on heading technique and head acceleration is recommended.

Preparation of 18O-labelled azaspiracids for accurate quantitation using liquid chromatography-mass spectrometry.

Azaspiracids (AZAs) are a group of polyether marine algal toxins known to accumulate in shellfish, posing a risk to human health and the seafood industry. Analysis of AZAs is typically performed using LC-MS, which can suffer from matrix effects that significantly impact the accuracy of measurement results. While the use of isotopic internal standards is an effective approach to correct for these effects, isotopically labelled standards for AZAs are not currently available. In this study, 18O-labelled AZA1, AZA2, and AZA3 were prepared by reaction with H218O under acidic conditions, and the reaction kinetics and sites of incorporation were studied using LC-HRMS/MS aided by mathematical analysis of their isotope patterns. Analysis of the isotopic incorporation in AZA1 and AZA3 indicated the presence of four exchangeable oxygen atoms. Excessive isomerization occurred during preparation of 18O-labelled AZA2, suggesting a role for the 8-methyl group in the thermodynamic stability of AZAs. Neutralized mixtures of 18O-labelled AZA1 and AZA3 were found to maintain their isotopic and isomeric integrities when stored at -20 °C and were used to develop an isotope-dilution LC-MS method which was applied to reference materials of shellfish matrices containing AZAs, demonstrating high accuracy and excellent reproducibility. Preparation of isotopically labelled compounds using the isotopic exchange method, combined with the kinetic analysis, offers a feasible way to obtain isotopically labelled internal standards for a wide variety of biomolecules to support reliable quantitation.

Integrating biomechanics with stakeholder perspectives to inform safety in grassroots dirt track racing.

Grassroots dirt track racing is a foundational part of motorsports with a high risk of severe injury. This study aimed to gather perspectives and experiences of motorsports drivers surrounding safety and head acceleration events experienced during grassroots dirt track racing to inform strategies to improve driver safety. Thirteen drivers (n=9 who primarily race on dirt tracks; n=4 who primarily race on pavement tracks) with prior dirt track racing experience participated in separate, group-specific focus groups and/or one-on-one interviews where video, simulations of head motion, and head acceleration data were shared. Peak kinematics of laps and crash contact scenarios were recorded, and head perturbations (i.e., deviations in head motion relative to its moving-average trajectory) were quantified for each lap and presented through guided discussion. Responses were summarized using Rapid Assessment Process. Audio recordings and field notes were collected from focus groups and interviews and analyzed across 25 domains. Drivers described dirt track racing as short, fast bursts of racing. Benefits of dirt track racing for driver development were described, including learning car control. Drivers acknowledged risks of racing and expressed confidence in safety equipment but identified areas for improvement. Drivers observed lateral bouncing of the head in video and simulations but recognized that such motions were not noticed while racing. Track conditions and track type were identified as factors influencing head perturbations. Mean PLA (5.5 g) and PRV (3.07 rad/s) of perturbations experienced during racing laps and perturbation frequencies of 5 and 7 perturbations per second were reported. Generally, drivers accurately estimated the head acceleration magnitudes but were surprised by the frequency and maximum magnitude of perturbations. Maximum perturbation magnitudes (26.8 g and 19.0 rad/s) were attributed to hitting a "rut" in the dirt. Drivers described sudden stops, vertical loads due to landing from a large height, and impacts to the vehicle frame as crash events they physically feel the most. Summary statistics for crashes (medians = 7.30 g, 6.94 rad/s) were reported. Typical impact magnitudes measured in other sports (e.g., football) were provided for context. Upon reviewing the biomechanics, drivers were surprised that crash accelerations were relatively low compared to other contact/collision sports. Pavement drivers noted limited safety features in dirt track racing compared to pavement, including rigidity of vehicle frames, seat structure, seatbelt integration, and lack of oversight from sanctioning bodies. Most drivers felt seat inserts and head and neck restraints are important for injury prevention; however, usage of seat inserts and preferred head and neck restraint system differed among drivers. Drivers described their perspectives and experiences related to safety and identified strategies to improve safety in grassroots dirt track racing. Drivers expressed support for future safety research.

Liquid chromatography-high-resolution tandem mass spectrometry of anatoxins, including new conjugates and reduction products.

Anatoxins (ATXs) are a potent class of cyanobacterial neurotoxins for which only a handful of structural analogues have been well characterized. Here, we report the development of an LC-HRMS/MS method for the comprehensive detection of ATXs. Application of this method to samples of benthic cyanobacterial mats and laboratory cultures showed detection of several new ATXs. Many of these result from nucleophilic addition to the olefinic bond of the α,ß-unsaturated ketone functional group of anatoxin-a (ATX) and homoanatoxin-a (hATX), analogous to the conjugation chemistry of microcystins, which contain similar α,ß-unsaturated amide functionality. Conjugates with glutathione, γ-glutamylcysteine, methanethiol, ammonia, methanol and water were detected, as well as putative C-10 alcohol derivatives. Structural confirmation was obtained by simple and selective analytical-scale semisynthetic reactions starting from available ATX standards. Methanol, water and ammonia conjugates were found to result primarily from sample preparation. Reduction products were found to result from enzymatic reactions occurring primarily after cell lysis in laboratory cultures of Kamptonema formosum and Cuspidothrix issatschenkoi. The relative contributions of the identified analogues to the anatoxin profiles in a set of 22 benthic-cyanobacterial-mat field samples were estimated, showing conjugates to account for up to 15% of total ATX peak area and 10-hydroxyanatoxins up to 38%. The developed methodology, new analogues and insight into the chemical and enzymatic reactivity of ATXs will enable a more comprehensive study of the class than possible previously.

Driver head kinematics in grassroots dirt track racing crashes: A pilot analysis.

Motorsport athletes experience head acceleration loading during crashes; however, there is limited literature quantifying the frequency and magnitude of these loads, particularly at the grassroots level of the sport. Understanding head motion experienced during crash events in motorsport is necessary to inform interventions to improve driver safety. This study aimed to quantify and characterize driver head and vehicle kinematics during crashes in open-wheel grassroots dirt track racing. Seven drivers (ages 16-22, n = 2 female) competing in a national midget car series were enrolled in this study over two racing seasons and were instrumented with custom mouthpiece sensors. Drivers' vehicles were outfitted with an incident data recorder (IDR) to measure vehicle acceleration. Forty-one crash events were verified and segmented into 139 individual contact scenarios via film review. Peak resultant linear acceleration (PLA) of the vehicle and PLA, peak rotational acceleration (PRA), and peak rotational velocity (PRV) of the head were quantified and compared across the part of the vehicle contacted (i.e., tires or chassis), the vehicle location contacted (e.g., front, left, bottom), the external object contacted (i.e., another vehicle, wall, or the track), and the principal direction of force (PDOF). The median (95th percentile) PLA, PRA, and PRV of the head and PLA of the vehicle were 12.3 (37.3) g, 626 (1799) rad/s2, 8.92 (18.6) rad/s, and 23.2 (88.1) g, respectively. Contacts with a non-horizontal PDOF (n = 98, 71%) and contact with the track (n = 96, 70%) were common in the data set. Contact to the left side of the vehicle, with the track, and with a non-horizontal PDOF tended to have the greatest head kinematics compared to other factors in each sub-analysis. Results from this pilot study can inform larger studies of head acceleration exposure during crashes in the grassroots motorsports environment and may ultimately support evidence-based driver safety interventions.

Coarse-grained dynamics of transiently bound fast linkers.

Transient bonds between fast linkers and slower particles are widespread in physical and biological systems. Despite their diverse structure and function, a commonality is that the linkers diffuse on timescales much faster compared to the overall motion of the particles they bind to. This limits numerical and theoretical approaches that need to resolve these diverse timescales with high accuracy. Many models, therefore, resort to effective, yet ad hoc, dynamics, where linker motion is only accounted for when bound. This paper provides a mathematical justification for such coarse-grained dynamics that preserves detailed balance at equilibrium. Our derivation is based on multiscale averaging techniques and is broadly applicable. We verify our results with simulations on a minimal model of fast linker binding to a slow particle. We show how our framework can be applied to various systems, including those with multiple linkers, stiffening linkers upon binding, or slip bonds with force-dependent unbinding. Importantly, the preservation of detailed balance only sets the ratio of the binding to the unbinding rates, but it does not constrain the detailed expression of binding kinetics. We conclude by discussing how various choices of binding kinetics may affect macroscopic dynamics.

Stochastic switching of delayed feedback suppresses oscillations in genetic regulatory systems.

Delays and stochasticity have both served as crucially valuable ingredients in mathematical descriptions of control, physical and biological systems. In this work, we investigate how explicitly dynamical stochasticity in delays modulates the effect of delayed feedback. To do so, we consider a hybrid model where stochastic delays evolve by a continuous-time Markov chain, and between switching events, the system of interest evolves via a deterministic delay equation. Our main contribution is the calculation of an effective delay equation in the fast switching limit. This effective equation maintains the influence of all subsystem delays and cannot be replaced with a single effective delay. To illustrate the relevance of this calculation, we investigate a simple model of stochastically switching delayed feedback motivated by gene regulation. We show that sufficiently fast switching between two oscillatory subsystems can yield stable dynamics.

Head Impact Exposure in Female Collegiate Soccer by Activity Type.

Soccer, one of the most popular sports in the world, has one of the highest rates of sports-related concussions. Additionally, soccer players are frequently exposed to nonconcussive impacts from intentionally heading the ball, a fundamental component of the sport. There have been many studies on head impact exposure in soccer, but few focus on soccer practices or practice activities. This study aimed to characterize the frequency and magnitude of head impacts in National Collegiate Athletic Association Division I female soccer practice activities using a custom-fit instrumented mouthpiece. Sixteen players were instrumented over the course of 54 practice sessions. Video analysis was performed to verify all mouthpiece-recorded events and classify practice activities. Category groupings of practice activities include technical training, team interaction, set pieces, position-specific, and other. Differences in head impact rates and peak resultant kinematics were observed across activity types and category groupings. Technical training had the highest impact rate compared to other category groupings. Impacts occurring during set piece activities had the highest mean kinematic values. Understanding drill exposure can help inform coaches on training plans aimed to reduce head impact exposure for their athletes.

Characterization of Head Acceleration Exposure During Youth Football Practice Drills.

Many head acceleration events (HAEs) observed in youth football emanate from a practice environment. This study aimed to evaluate HAEs in youth football practice drills using a mouthpiece-based sensor, differentiating between inertial and direct HAEs. Head acceleration data were collected from athletes participating on 2 youth football teams (ages 11-13 y) using an instrumented mouthpiece-based sensor during all practice sessions in a single season. Video was recorded and analyzed to verify and assign HAEs to specific practice drill characteristics, including drill intensity, drill classification, and drill type. HAEs were quantified in terms of HAEs per athlete per minute and peak linear and rotational acceleration and rotational velocity. Mixed-effects models were used to evaluate the differences in kinematics, and generalized linear models were used to assess differences in HAE frequency between drill categories. A total of 3237 HAEs were verified and evaluated from 29 football athletes enrolled in this study. Head kinematics varied significantly between drill categorizations. HAEs collected at higher intensities resulted in significantly greater kinematics than lower-intensity drills. The results of this study add to the growing body of evidence informing evidence-based strategies to reduce head impact exposure and concussion risk in youth football practices.