Neuromuscular Fatigue and Biomechanical Alterations during High-Intensity, Constant-Load Cycling

Neuromuscular fatigue is an inevitable process at play during prolonged exercise, and may be caused by multiple alterations within the central nervous system and peripheral musculature. As fatigue develops, the neuromuscular system must adapt to these changes by making compensatory movement pattern adjustments so as to use motor pathways that are less fatigued in an effort to maintain task performance; motor variability is thus increased. The primary purpose of the four studies contained within this doctoral thesis was to detail the progression of exercise-induced neuromuscular fatigue, and to improve our understanding of the muscle activation and joint kinematic alterations that occur as fatigue accumulates. Within this context, cycling was used as the exercise model, and the relationship between physiological and biomechanical aspects of high-intensity, moderate duration (\u3c10 \u3emin) cycling were specifically examined. The first two studies of this thesis were aimed at understanding the progression of neuromuscular fatigue as well as the associated motor control and biomechanical (i.e. muscle activation and kinematic) changes that occur during exhaustive cycling. Specifically, the time course and relative contributions of central and peripheral fatigue mechanisms, and the associated changes in muscle activation and both lower (i.e. hip, knee and ankle joint) and upper (i.e. trunk) limb kinematics were examined during a high-intensity cycling time to exhaustion (TTE) test. This was performed at 90% maximal aerobic power (Pmax) with nine well-trained cyclists. Temporal relationships between joint kinematics and changes in markers of central and peripheral fatigue were also examined. Peripheral fatigue (i.e. impaired contractile function: reduced peak twitch torque, −39.9%; twitch contraction time, −10.7%; and the average rates of twitch torque development −34.7% and relaxation −36.7% at task failure i.e., T100) developed early in the exercise bout from 60% of the time to task failure (p \u3c 0.05). However, a central facilitation, measured as an increase in peak vastus medialis (38.9%) and gluteus maximus electromyogram (87.2%) amplitudes at T100, rather than central fatigue, occurred towards the end of the exercise task (p \u3c 0.05). Thus, neuromuscular fatigue development was associated with an increase in the magnitude of lower limb muscle activity, which may have represented an attempt to increase muscle force to maintain the required power output of the cycling task. Increases in trunk flexion were observed from 60% of the time to task failure (p \u3c 0.05), and were therefore notable at or after the point of significant peripheral fatigue. Conversely, increases in trunk medio-lateral sway (lateral flexion), hip abduction/adduction and knee valgus/varus were observed only from 80% of the time to task failure (p \u3c 0.05), which paralleled the increase in central motor drive. The results of this study therefore indicate that significant trunk kinematic changes in the sagittal plane occurred at or after the point of significant peripheral fatigue development, whereas, significant changes at the trunk, hip and knee joints in the coronal plane occurred later in the exercise task and paralleled the facilitation of central motor drive during the cycling task. In the third study, the effects of real-time, kinematic feedback provision for trunk flexion (TTETflex), trunk medio-lateral sway (TTETsway) and hip abduction/adduction (TTEHabd/add) during a high-intensity TTE cycling test (90% Pmax) in nine well-trained cyclists were examined. The times taken to reach task failure were compared to a TTE test completed with no feedback. The times taken to reach task failure were not significantly different when provided with trunk flexion (TTETflex) and hip abduction/adduction (TTEHabd/add) feedback compared to the non-feedback condition (p \u3e 0.05). There was, however, a significant decrease in the time to task failure during the TTETsway test (p \u3c 0.05). Not all participants could maintain trunk and/or hip movement within a set movement pattern criteria; and three participants were therefore excluded from the kinematic analyses for both the TTETflex and TTETsway tests (n = 6) as were two participants from the TTEHabd/add test (n = 7). For participants who correctly used the kinematic feedback, no differences in the times taken to reach failure were observed in between the feedback (TTETflex, TTETsway and TTEHabd/add) and nonfeedback test conditions (p \u3e 0.05). Despite being given feedback, changes in joint kinematics were similar across all test conditions; significant alterations were observed at the trunk and knee joints in the sagittal plane and at the hip and knee joints in the coronal plane (p \u3c 0.05). Given trunk flexion feedback (TTETflex), significant increases in left hip flexion and trunk medio-lateral sway ROM were observed (p \u3c 0.05), whereas given trunk medio-lateral sway feedback (TTETsway), increases in right hip flexion ROM also occurred (p \u3c 0.05). These results indicate that, regardless of whether or not well-trained cyclists are able to control the level of kinematic variability when fatigued, acute exposure to real-time kinematic feedback to limit trunk or hip movement during high-intensity cycling may influence cycling kinematics (i.e. technique) and, in some cases (e.g. trunk medio-lateral sway), may reduce performance. The final study examined the relationship between joint kinematics, measured in non-fatigued and fatigued high-intensity cycling, and the cyclists’ physiological profiles (i.e., physiological attributes indicative of successful cycling ability, including both maximal oxygen consumption and peak power output relative to body mass, maximal heart rate, both power output and heart rate at the first and second ventilatory thresholds and cycling economy at 100 W) and the time taken to reach task failure. Submaximal physiological attributes were correlated with hip (abduction/adduction angle and ROM), knee (flexion angle) and ankle (flexion ROM) kinematics measured in a non-fatigued state at the start of the trial (r \u3e 0.40; p \u3c 0.05). However, both physiological attributes associated with maximal exercise capacity and cycling economy were correlated with trunk (flexion angle) and ankle (flexion angle and ROM) kinematics measured in a fatigued state at the end of the test (r \u3e 0.40; p \u3c 0.05). Trunk flexion and medio-lateral sway ROM in a non-fatigued state, and trunk flexion angle in a fatigued state, were associated with the time to task failure (r \u3e 0.50; p \u3c 0.05). Thus, the degree of trunk flexion and medio-lateral sway may be important kinematic variables that are indicative of cycling performance. These findings reveal an interdependence between cycling kinematics and both the physiological attributes indicative of successful cycling performance and the time taken to reach task failure during high-intensity, constant-load cycling. In conclusion, the findings presented in this thesis indicate that the temporal patterns of central and peripheral neuromuscular fatigue differ (Study 1; Chapter 3). Task failure during high intensity cycling appears to be associated with the development of peripheral fatigue despite the presence of an increase in central motor drive. Subsequent to the development of neuromuscular fatigue, muscle activation and joint kinematic alterations can be observed, which may represent compensatory mechanisms employed by the neuromuscular system to continue task performance (Studies 1 and 2; Chapters 3 and 4). Joint kinematic alterations in the sagittal plane were associated with the development of peripheral fatigue whereas coronal plane adjustments occurred in parallel with central facilitation, and/or when a more substantial level of peripheral fatigue accumulated. Such compensatory kinematic strategies are also associated with an athlete’s physiological attributes and their cycling performance (i.e., time to task failure) (Study 4; Chapter 6). Importantly, imposing specific joint kinematic restrictions (trunk flexion, trunk medio-lateral sway and hip abduction/adduction) during exhaustive cycling, influenced cycling kinematics (i.e. technique) and, in some cases (e.g. trunk medio-lateral sway), reduced the time taken to reach task failure for well-trained cyclists (Study 3; Chapter 5). Such findings enhance our understanding of how the neuromuscular system copes with fatigue development, and should assist coaches and/or occupational health practitioners to better understand the fatigue process and neuromuscular strategies utilised during exercise tasks with similar characteristics to that used in the current studies

Home Modification and Repairs for Older Adults: Challenges and Opportunities for State Units on Aging

The home environment plays a critical role in adults' ability to stay in their homes and communities as they age, commonly referred to as aging in place. Yet the majority of older adults' homes lack supportive features. Home modification is the process of making changes to a home to increase independence, safety, and health. Often combined with related repairs, home modification and repair (HMR) can be minor, such as adding grab bars and removing tripping hazards, or major, such as installing roll-in showers and ramps. Although HMRs can support people as their needs change and even preclude moves to institutional settings, numerous barriers challenge the ability of older adults and caregivers to access them.In response, the Administration for Community Living (ACL) funded the University of Southern California (USC) Leonard Davis School of Gerontology to implement the project, "Promoting Aging in Place by Enhancing Access to Home Modifications." Its goal is to address the barriers to home modification access and service delivery by increasing the availability and awareness of home modification at the national, state, and local levels. A key activity of this project was to develop a knowledge base of state HMR activities and programs for older adults and persons with disabilities with a focus on the State Units on Aging (SUAs). These agencies develop and implement state plans and support services for older persons, adults with physical disabilities and their families. SUAs administer funds, including those provided through the Older Americans Act (OAA), to support HMR services through local Area Agencies on Aging (AAAs) and other state and local entities (e.g., OAA Title VI organizations that serve older Native Americans). SUAs can play a significant role in HMR by including it in state plans, providing designated funding, raising awareness, and coordinating with other state agencies such as housing, disability, and health.In October 2019, USC and its ACL project partner ADvancing States administered an online survey of directors of the 56 SUAs (which ADvancing States represents). The 10-question closed and open-ended survey sought to ascertain SUA activities, challenges, and opportunities in HMR. With extensive follow-up through February 2020, 50 SUAs completed the survey (an 89% response rate).This report summarizes the survey results, giving a bird's eye view of SUA roles in HMR and shining a light on examples of SUA HMR activities. Its purpose is to encourage greater involvement and coordination in HMR service delivery among agencies with a stake in assuring older Americans' ability to age in place.Click "Download" to access this resource.Tags: Older Americans Act, Area Agencies on Aging, State Units on Aging, Home-and Community-Based Service

Good prospects: high-resolution telemetry data suggests novel brood site selection behaviour in waterfowl

Breeding success should increase with prior knowledge of the surrounding environment, which is dependent upon an animal\u27s ability to evaluate habitat. Prospecting for nesting locations and migratory stopover sites are well-established behaviours among bird species. We assessed whether three species of California dabbling ducks – mallards, Anas platyrhynchos, gadwall, Mareca strepera, and cinnamon teal, Spatula cyanoptera – in Suisun Marsh, California, U.S.A., a brackish marsh, prospect for suitable wetlands in the week prior to brooding. K-means cluster analyses grouped 29 mallard and gadwall hens into three groups. One group (N = 13) demonstrated evidence of brood site prospecting, with the fewest and latest prebrooding wetland visits. Of these hens, seven visited their future brood pond an average of 1.14 times and only shortly before brooding (1.29 days), obtaining current information on habitat suitability. For the remaining six hens, we did not detect a brooding wetland visit, possibly due to data limitations or because these hens acquired sufficient familiarity with the wetland habitat during nest breaks in adjacent wetlands, obviating the need to prospect the specific brood pond. The second identified group of hens (N = 11) visited the brooding wetland most frequently (on 4.55 days), further in advance (5.27 days), with the fewest unique wetland visits and the earliest brooding date (26 May). The final group of hens (N = 5) were the latest to brood (21 June) and visited the most wetlands, possibly due to less water or more broods present across the landscape. Brood ponds were always farther from the nest than the nearest ponds, indicating that habitat suitability or presence of conspecifics is more important to brood site selection. Prospecting provides hens with knowledge about current habitat conditions and allows them to ‘crowdsource’ public information regarding use of that habitat by other brooding hens. Prospecting may, therefore, benefit ducks inhabiting ephemeral habitats like those within Suisun Marsh, where brood habitat is limited and water cover changes rapidly during the breeding season

Sources and Structures of Mitotic Crossovers That Arise When BLM Helicase Is Absent in Drosophila

The Bloom syndrome helicase, BLM, has numerous functions that prevent mitotic crossovers. We used unique features of Drosophila melanogaster to investigate origins and properties of mitotic crossovers that occur when BLM is absent. Induction of lesions that block replication forks increased crossover frequencies, consistent with functions for BLM in responding to fork blockage. In contrast, treatment with hydroxyurea, which stalls forks, did not elevate crossovers, even though mutants lacking BLM are sensitive to killing by this agent. To learn about sources of spontaneous recombination, we mapped mitotic crossovers in mutants lacking BLM. In the male germline, irradiation-induced crossovers were distributed randomly across the euchromatin, but spontaneous crossovers were nonrandom. We suggest that regions of the genome with a high frequency of mitotic crossovers may be analogous to common fragile sites in the human genome. Interestingly, in the male germline there is a paucity of crossovers in the interval that spans the pericentric heterochromatin, but in the female germline this interval is more prone to crossing over. Finally, our system allowed us to recover pairs of reciprocal crossover chromosomes. Sequencing of these revealed the existence of gene conversion tracts and did not provide any evidence for mutations associated with crossovers. These findings provide important new insights into sources and structures of mitotic crossovers and functions of BLM helicase

Mutation spectrum of NOD2 reveals recessive inheritance as a main driver of Early Onset Crohn’s Disease

Inflammatory bowel disease (IBD), clinically defined as Crohn’s disease (CD), ulcerative colitis (UC), or IBD-unclassified, results in chronic inflammation of the gastrointestinal tract in genetically susceptible hosts. Pediatric onset IBD represents ≥ 25% of all IBD diagnoses and often presents with intestinal stricturing, perianal disease, and failed response to conventional treatments. NOD2 was the first and is the most replicated locus associated with adult IBD, to date. However, its role in pediatric onset IBD is not well understood. We performed whole-exome sequencing on a cohort of 1,183 patients with pediatric onset IBD (ages 0–18.5 years). We identified 92 probands with biallelic rare and low frequency NOD2 variants accounting for approximately 8% of our cohort, suggesting a Mendelian inheritance pattern of disease. Additionally, we investigated the contribution of recessive inheritance of NOD2 alleles in adult IBD patients from a large clinical population cohort. We found that recessive inheritance of NOD2 variants explains ~ 7% of cases in this adult IBD cohort, including ~ 10% of CD cases, confirming the observations from our pediatric IBD cohort. Exploration of EHR data showed that several of these adult IBD patients obtained their initial IBD diagnosis before 18 years of age, consistent with early onset disease. While it has been previously reported that carriers of more than one NOD2 risk alleles have increased susceptibility to Crohn’s Disease (CD), our data formally demonstrate that recessive inheritance of NOD2 alleles is a mechanistic driver of early onset IBD, specifically CD, likely due to loss of NOD2 protein function. Collectively, our findings show that recessive inheritance of rare and low frequency deleterious NOD2 variants account for 7–10% of CD cases and implicate NOD2 as a Mendelian disease gene for early onset Crohn’s Disease

Preventing Falls in Older Californians: State of the Art

In February 2003, the Foundation convened over 150 leaders in academic, legislative, community-based services, consumer advocates, aging network, housing, public health, public safety, and other leaders who worked for two days on a statewide blueprint on fall prevention.  In preparation for the convening, a Preconference White Paper was created and used to build the blueprint.  The California Blueprint describes state-of-the-art approaches to reducing the risks of falls, and the challenges to implementing fall prevention in California.  One of the top recommendations from this blueprint was the creation of a coordination center that could serve as a statewide resource and lead efforts in fall prevention.  This recommendation eventually led to the creation of the Fall Prevention Center of Excellence (FPCE)

A Simple Standard for Sharing Ontological Mappings (SSSOM).

Despite progress in the development of standards for describing and exchanging scientific information, the lack of easy-to-use standards for mapping between different representations of the same or similar objects in different databases poses a major impediment to data integration and interoperability. Mappings often lack the metadata needed to be correctly interpreted and applied. For example, are two terms equivalent or merely related? Are they narrow or broad matches? Or are they associated in some other way? Such relationships between the mapped terms are often not documented, which leads to incorrect assumptions and makes them hard to use in scenarios that require a high degree of precision (such as diagnostics or risk prediction). Furthermore, the lack of descriptions of how mappings were done makes it hard to combine and reconcile mappings, particularly curated and automated ones. We have developed the Simple Standard for Sharing Ontological Mappings (SSSOM) which addresses these problems by: (i) Introducing a machine-readable and extensible vocabulary to describe metadata that makes imprecision, inaccuracy and incompleteness in mappings explicit. (ii) Defining an easy-to-use simple table-based format that can be integrated into existing data science pipelines without the need to parse or query ontologies, and that integrates seamlessly with Linked Data principles. (iii) Implementing open and community-driven collaborative workflows that are designed to evolve the standard continuously to address changing requirements and mapping practices. (iv) Providing reference tools and software libraries for working with the standard. In this paper, we present the SSSOM standard, describe several use cases in detail and survey some of the existing work on standardizing the exchange of mappings, with the goal of making mappings Findable, Accessible, Interoperable and Reusable (FAIR). The SSSOM specification can be found at http://w3id.org/sssom/spec. Database URL: http://w3id.org/sssom/spec

Using isoelectric point to determine the pH for initial protein crystallisation trials

The identification of suitable conditions for crystallization is a rate-limiting step in protein structure determination. The pH of an experiment is an important parameter and has the potential to be used in data-mining studies to help reduce the number of crystallisation trials required. However, the pH is usually recorded as that of the buffer solution, which can be highly inaccurate. Results: Here we show that a better estimate of the true pH can be predicted by considering not only the buffer pH but also any other chemicals in the crystallisation solution. We use these more accurate pH values to investigate the disputed relationship between the pI of a protein and the pH at which it crystallises

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe