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Williams, S. T.

Publications and source records attributed to Williams, S. T..

15 recordsLinked to original sources

Generic versus personalized foot-ground contact models for predictive simulations of walking: Is personalization worth the effort?

PurposeQuantification of walking function, including joint motions, ground reactions, and joint loads, outside the lab is a growing research area. Because only joint motions can currently be measured outside the lab, researchers are utilizing tracking optimizations of walking to estimate associated ground reactions and inverse dynamic joint loads. However, foot-ground contact models used in such optimizations have been generic rather than personalized, which may limit the accuracy of estimated ground reactions and joint loads. This study compares the predictive capabilities of generic versus personalized foot-ground contact models. MethodsGeneric and personalized foot-ground contact models were evaluated in calibration and tracking optimizations performed using experimental walking data collected from three subjects in varying states of health. Foot-only calibration optimizations evaluated how well both models could reproduce experimental ground reaction and foot motion data while tracking both types of data simultaneously, while whole-body tracking optimizations evaluated how well both models could reproduce experimental ground reactions, joint motion, and joint load data while tracking only experimental joint motion data and achieving dynamic consistency. ResultsFor all three subjects and both types of optimizations, personalized foot-ground contact models reproduced experimental ground reaction, joint motion, and joint load data more accurately than generic foot-ground contact models. ConclusionPersonalized foot-ground contact models can improve the accuracy with which ground reactions and joint loads can be estimated via tracking optimizations of walking using only experimental motion data as inputs. Personalized models require little time and effort to calibrate using freely available software tools and should improve the accuracy of predictive simulations of walking as well.

bioengineering↗

Synergy Feedback Control Predicts Walking Across Multiple Cycles

Neural feedback is important for the control of movement, and multiple neurological disorders (e.g., stroke, cerebral palsy, Parkinsons disease, incomplete spinal cord injury) are characterized by altered neural feedback. Researchers have created numerous computational neuromusculoskeletal models controlled by simulated neural feedback mechanisms, but these models rarely represent actual human subjects and thus have not found practical clinical application. As a step toward designing patient-specific treatments for individuals with neurological disorders, this study used the Neuromusculoskeletal Modeling Pipeline to develop and evaluate a novel synergy-based feedforward (FF)+feedback (FB) control model using a personalized three-dimensional neuromusculoskeletal walking model of an actual human subject post-stroke. Experimental walking data collected from the subject were used to create the subjects personalized walking model. Then for 5 calibration walking cycles, personalized synergy-based FF+FB control models were created. First, the personalized model was used to estimate lower body muscle activations consistent with the subjects electromyographic, joint motion, and joint moment data. Second, five synergy activations per leg with associated synergy vectors were calculated that closely reconstructed the subjects muscle activations and joint moments simultaneously. Third, nominal FF synergy activation controls were calculated by averaging the synergy activations for each leg. Fourth, the nominal FF synergy controls were scaled by 0, 25, 50, 75, 100, and 125%, and the gap in reproducing the subjects muscle activations was filled by fitting FB synergy activation controls as a function of joint positions, velocities, and moments as surrogates for muscle lengths, muscle velocities, and tendon forces. Next for 3 testing walking cycles, the six synergy-based FF+FB models were used to control the subjects personalized walking model in predictive simulations. The 100% FF model (which still had minimal FB) reproduced the testing walking cycles the most closely, and only the 75%, 100%, and 125% FF models predicted near-periodic walking motions using initial conditions consistent with experimental values. The 0, 25, and 50% FF models could generate near-periodic walking motions only when the initial conditions were allowed to diverge substantially from experimental values. Our findings suggest that predictive simulations of walking may require substantial feedforward control when modeling an actual human subject.

bioengineering↗

Reproducible Research: Computational Design of PersonalizedClinical Treatments for Walking Impairments Using the Neuromusculoskeletal Modeling Pipeline

Background: Personalized computational neuromusculoskeletal models have great potential for optimizing the design of clinical treatments for movement impairments. While many software tools address specific parts of the model personalization and treatment optimization processes, they typically require significant programming experience to use and do not cover the full breadth of these two processes. Furthermore, published neuromusculoskeletal modeling studies typically do not provide all the methodological details needed for others to reproduce the work. Consequently, researchers seeking to develop skills in the model personalization and treatment optimization processes face a steep learning curve due to the lack of detailed training materials that demonstrate both processes for real-life clinical problems using real-life subject movement data. Methods: This article presents detailed training tutorials for the model personalization and treatment optimization processes using two real-life clinical problems and the Neuromusculoskeletal Modeling (NMSM) Pipeline. The first clinical problem involves the design of personalized gait modifications and high tibial osteotomy surgery for an individual with bilateral medial knee osteoarthritis, where the goal is to reduce the peak adduction moment in both knees to a specified target level. The second clinical problem involves the design of a synergy-based functional electrical stimulation prescription for an individual post-stroke with impaired walking function, where the goal is to equalize the propulsive and braking impulses between the two legs. Both tutorials were implemented as course projects given to novice users in a combined undergraduate/graduate mechanical engineering course. Results: Both tutorials produced personalized neuromusculoskeletal models and associated dynamically consistent tracking optimizations that closely reproduced subject-specific experimental joint angles, joint moments, ground reaction forces and moments, and (if applicable) muscle activations measured during walking. Subsequent design optimizations predicted personalized treatments that achieved target values of peak knee adduction moments or propulsive and braking impulses. Conclusions: The detailed step-by-step tutorials presented with this article are the first to walk users through the entire process of creating personalized neuromusculoskeletal models and then using them to design personalized treatments for two subjects with two different clinical problems. These tutorials can be used to introduce new users to the NMSM Pipeline and as projects in neuromusculoskeletal modeling courses.

bioengineering↗

Rare shell colours in bivalves reveal multiple evolutionary pathways to blue and green colouration

Green and blue are rare colours in bivalve shells. Where such colours occur, it is unclear whether they result from shared pigments across taxa, as similar appearances may arise from different compounds and are not necessarily homologous. Identifying their biochemical basis is therefore crucial to understanding the evolution and possible metabolic costs of these unusual traits. We used Raman spectroscopy to analyse resin-embedded cross-sections of valves from 15 bivalve species with green or blue shells. Species represented diversity in shell colour in terms of both phylogeny and morphological traits, including colour location (organic periostracum, organic layers in the calcareous shell or inorganic calcareous matrix). Green colour consistently occurred in organic layers rather than calcareous shell, while blue colour occurs in both calcareous shell and organic layers. Blue colour appears to be due to carotenoid-based pigments, similar to other pigments observed in bivalve shells. Green colour, however, is due either to novel pigments, not previously identified in mollusc shells, which are only weakly Raman active or nanostructures that produce structural colour in the absence of green pigments. Within bivalves, to date structural colour has been reported only in one genus, underscoring its evolutionary significance.

evolutionary biology↗

Tropicalisation of rocky shore gastropod communities along the Baja California Peninsula

Tropicalisation is rapidly restructuring marine communities globally. Despite extensive research in subtidal habitats, the extent of tropicalisation and its impact on rocky intertidal communities remains poorly understood. Here we integrated contemporary field surveys with genetic barcoding, historic surveys, museum collections, and fossil records to document changes in the rocky shore gastropod communities along 8 degrees of latitude (approximately 3,120 km of coastline) of the Baja California Peninsula. We detected poleward range expansions of 30 tropical and subtropical species, and trailing-edge retractions of 13 temperate species, with some range shifts occurring across long-standing biogeographic boundaries. Fossil evidence reveals that several range-extending species previously occupied latitudes beyond their modern distributions during Pleistocene warm periods, suggesting that contemporary expansions echo historical responses to climatic warming, albeit under accelerated rates. Using Lottia gigantea as a case study, we demonstrated early range retractions can be marked by shifts in size-frequency distributions demonstrating declines in abundance, and loss of small individuals suggestive of reduced recruitment. We showed that rocky intertidal systems are sensitive to climate-driven range shifts, and highlighted the importance of integrating historical, palaeontological and contemporary data to detect early ecological and evolutionary consequences of tropicalisation. Continued monitoring combined with molecular approaches is crucial for predicting and managing biodiversity responses under ongoing climate change.

ecology↗

The genome of the charismatic sea star Linckia laevigata

Linckia laevigata is a tropical sea star commonly found throughout the Indian and Pacific Oceans, and is one of the top ten-most collected invertebrates, often encountered in the aquarium trade. It has been the subject of investigations into population structure, biodiversity and ecology, particularly regarding gene flow among populations throughout its range, the status of different colour morphs and its relationship with its putative sister species, L. multifora. Here we present and describe a high-quality genome assembly for L. laevigata. Our assembly is 585.97 Mb in length, with a scaffold N50 of 3 Mb. The genome has a typical repeat (36.99%) and GC content (41.33%), when compared with other echinoderm datasets. Our genome annotation recovers 16,178 genes, with high (89.4%) recovery of the metazoan BUSCO set. This novel resource will provide a model organism for studying the biogeography of the tropical Indo-West Pacific region, and more specifically facilitate the investigation of a range of sea star traits at the genomic level. SignificanceSea stars remain poorly characterised at a genomic level. Data from the charismatic tropical sea star Linckia laevigata will enable future studies into the biology, population structure and evolution of these ecologically important species.

genetics↗

Auranofin Inhibits Hepatitis E Virus Replication Via Reactive Oxygen Species

Hepatitis E virus (HEV) causes roughly 20 million yearly global infections, and is associated with chronic hepatitis, neurological sequelae and pregnancy-related adverse outcomes that require antiviral therapeutic intervention. While there are currently no approved HEV-specific therapeutics, ribavirin and pegylated interferon, prescribed off-label, are the current standard of care. However, ribavirin resistance and toxicity highlight the unmet clinical need to identify safer, HEV-specific antivirals. Auranofin, an FDA-approved anti-rheumatic drug, displays antiviral activity against several viruses. Therefore, we investigated auranofins potential as an antiviral and its mechanism of action against HEV. We demonstrated that auranofin displays dose-dependent antiviral activity against two genotypes of HEV that cause a significant proportion of human disease, as well as against a ribavirin treatment failure-associated mutant. Because auranofin is known to increase reactive oxygen species (ROS), we investigated the antiviral mechanism of action via treatment with ROS inhibitors. ROS inhibitors reversed auranofin-mediated ROS promotion and antiviral activity, suggesting the observed antiviral effects are mediated by ROS. Furthermore, treatment with a different ROS promotor, D-amino acid oxidase (DAAO), also displays antiviral activity against HEV, which was also reversed by treatment with a ROS inhibitor, suggesting that ROS accumulation alone is antiviral. We also demonstrated that combined treatment with auranofin and ribavirin exhibits synergistic antiviral activity in vitro, which supports repurposing auranofin as an antiviral against HEV, potentially in combination with ribavirin. Overall, this study has important implications in repurposing auranofin as an antiviral against HEV and in delineating the mechanism of action against HEV via ROS. ImportanceHepatitis E virus (HEV) lacks approved antiviral therapies, and off-label treatments are limited by toxicity and emerging resistance. This study identifies the FDA-approved drug auranofin as an effective in vitro inhibitor of HEV, including two globally relevant human-associated genotypes and a ribavirin treatment failure-associated mutant. Auranofins activity highlights the therapeutic potential of host-targeting antivirals, particularly those that promote the generation of reactive oxygen species, in treating HEV infection. These findings support further in vivo investigations of auranofin as a treatment for HEV and suggest that modulating host redox pathways by promoting reactive oxygen species may represent a promising strategy for broad-spectrum antiviral development.

microbiology↗

The Neuromusculoskeletal Modeling Pipeline: MATLAB-based Model Personalization and Treatment Optimization Functionality for OpenSim

Neuromusculoskeletal injuries including osteoarthritis, stroke, spinal cord injury, and traumatic brain injury affect roughly 19% of the U.S. adult population. Standardized interventions have produced suboptimal functional outcomes due to the unique treatment needs of each patient. Strides have been made to utilize computational models to develop personalized treatments, but researchers and clinicians have yet to cross the "valley of death" between fundamental research and clinical usefulness. This article introduces the Neuromusculoskeletal Modeling (NMSM) Pipeline, two MATLAB-based toolsets that add Model Personalization and Treatment Optimization functionality to OpenSim. The two toolsets facilitate computational design of individualized treatments for neuromusculoskeletal impairments through the use of personalized neuromusculoskeletal models and predictive simulation. The Model Personalization toolset contains four tools for personalizing 1) joint structure models, 2) muscle-tendon models, 3) neural control models, and 4) foot-ground contact models. The Treatment Optimization toolset contains three tools for predicting and optimizing a patients functional outcome for different treatment options using a patients personalized neuromusculoskeletal model with direct collocation optimal control methods. Support for user-defined cost functions and model modification functions facilitate simulation of a vast number of possible treatments. An NMSM Pipeline use case is presented for an individual post-stroke with impaired walking function, where the goal was to predict how the subjects neural control could be changed to improve walking speed without increasing metabolic cost. First the Model Personalization toolset was used to develop a personalized neuromusculoskeletal model of the subject starting from a generic OpenSim full- body model and experimental walking data (video motion capture, ground reaction, and electromyography) collected from the subject at his self-selected speed. Next the Treatment Optimization toolset was used with the personalized model to predict how the subject could recruit existing muscle synergies more effectively to reduce muscle activation disparities between the paretic and non-paretic legs. The software predicted that the subject could increase his walking speed by 60% without increasing his metabolic cost per unit time by modifying existing muscle synergy recruitment. This hypothetical treatment demonstrates how NMSM Pipeline tools could allow researchers working collaboratively with clinicians to develop personalized neuromusculoskeletal models of individual patients and to perform predictive simulations for the purpose of designing personalized treatments that maximize a patients post-treatment functional outcome.

bioengineering↗

Molecular phylogenetics of the superfamily Stromboidea (Caenogastropoda): new insights from increased taxon sampling

The superfamily Stromboidea is a clade of morphologically distinctive gastropods which include the iconic Strombidae, or true conchs. In this study, we present the most taxonomically extensive phylogeny of the superfamily to date, using fossil calibrations to produce a chronogram and extant geographical distributions to reconstruct ancestral ranges. From these results, we confirm the monophyly of all stromboidean families; however, six genera are not monophyletic using current generic assignments (Strombidae: Lentigo, Canarium, Dolomena, Doxander; Xenophoridae: Onustus, Xenophora). Within Strombidae, analyses resolve an Indo-West Pacific (IWP) clade sister to an East Pacific/Atlantic clade, together sister to a second, larger IWP clade. Our results also indicate two pulses of strombid diversification within the Miocene, and a Tethyan/IWP origin for Strombidae - both supported by the fossil record. However, conflicts between divergence time estimates and the fossil record warrant further exploration. Species delimitation analyses using the COI barcoding gene support several taxonomic changes. We synonymise Euprotomus aurora with Euprotomus bulla, Strombus alatus with Strombus pugilis, Dolomena abbotti with Dolomena labiosa, and Dolomena operosa with Dolomena vittata. We identified cryptic species complexes within Terebellum terebellum, Lambis lambis, "Canarium" wilsonorum, Dolomena turturella and Maculastrombus mutabilis. We reinstate Rimellopsis laurenti as a species (previously synonymised with R. laurenti) and recognise Harpago chiragra rugosus and Lambis truncata sowerbyi valid at the rank of species. Finally, we establish several new combinations, rendering Lentigo, Dolomena, and Canarium monophyletic: Lentigo thersites, Dolomena robusta, Dolomena epidromis, Dolomena turturella, Dolomena taeniata, Dolomena vanikorensis, D. vittata, "Canarium" wilsonorum, Hawaiistrombus scalariformis, Maculastrombus mutabilis, Maculastrombus microurceus.

zoology↗

Evolution of Large Eyes in Stromboidea (Gastropoda): Impact of Photic Environment and Life History Traits

AO_SCPLOWBSTRACTC_SCPLOWEyes within the marine gastropod superfamily Stromboidea range widely in size, from 0.2 to 2.3 mm, the latter being the largest known eyes of any gastropod. However, the evolutionary pressures underlying this variation remain unknown. Here, we use the wealth of material available in museum collections to explore the impact of ecological factors that affect light availability (ocean depth, turbidity and diel activity) on the evolution of eye size and structure within Stromboidea. We construct the most taxonomically extensive phylogeny of Stromboidea to date as a framework to investigate these relationships. Our results suggest that depth is a key light-limiting factor in stromboid eye evolution; here, increasing water depth is correlated with increasing aperture width relative to lens diameter (p = 0.043), and therefore an increasing investment in sensitivity in dim light environments. In the clade containing all large-eyed families (Strombidae, Rostellariidae and Seraphsidae), cathemeral species had wider eye apertures relative to lens sizes than diurnal species (p = 0.002), thereby prioritising sensitivity over resolution. These cathemeral species also had smaller body sizes than diurnal species (p = 0.002); this may suggest that animals with smaller shells are more vulnerable to shell-crushing predators, and therefore avoid the higher predation pressure experienced by animals active during the day. Within the large-eyed stromboid clade, ancestral state reconstruction estimates that absolute eye size increased above 1 mm twice independently. Due to the high energetic investment associated with large eye sizes, this repeated increase in eye size suggests that higher performance vision is important in behavioural tasks within these families. In addition, we note that species with more robust escape responses tend to have larger eyes than those that do not: for example, strombids have 1.79 {+/-} 0.31 times the eye size that would be expected from their body size (based on Stromboidea as a whole) and are known to display either a rapid escape response from an approaching predator or withdrawal into the shell. By contrast, the small-eyed xenophorids have 0.59 {+/-} 0.30 times the expected eye size, and are only known to withdraw when threatened.

evolutionary biology↗

The marine gastropod Conomurex luhuanus (Strombidae) has high-resolution spatial vision and eyes with complex retinas

All species within the conch snail family Strombidae possess large camera-type eyes that are surprisingly well-developed compared to those found in most other gastropods. Although these eyes are known to be structurally complex, very little research on their visual function has been conducted. Here, we use isoluminant expanding visual stimuli to measure the spatial resolution and contrast sensitivity of a strombid, Conomurex luhuanus. Using these stimuli, we show that this species responds to objects as small as 1.06{degrees} in its visual field. We also show that C. luhuanus responds to Michelson contrasts of 0.07, a low contrast sensitivity between object and background. The defensive withdrawal response elicited by visual stimuli of such small angular size and low contrast suggests that conch snails may use spatial vision for the early detection of potential predators. We support these findings with morphological estimations of spatial resolution of 1.04 {+/-} 0.14{degrees}. These anatomical data therefore agree with the behavioural measures and highlight the benefits of integrating morphological and behavioural approaches in animal vision studies. Furthermore, using contemporary imaging techniques including serial block-face scanning electron microscopy (SBF-SEM), in conjunction with transmission electron microscopy (TEM), we found that C. luhuanus have more complex retinas, in terms of cell type diversity, than previous studies of the group have discovered using TEM alone. We found the C. luhuanus retina is comprised of six cell types, including a newly identified ganglion cell and accessory photoreceptor, rather than the previously described four cell types. Summary statementBehavioural trials indicate the eyes of conch snail species Conomurex luhuanus provide high-resolution spatial vision, and morphological examination reveals the retina contains more cell types than those of other gastropods.

ecology↗

The Gene-Rich Genome of the Scallop Pecten maximus

BackgroundThe King Scallop, Pecten maximus, is distributed in shallow waters along the Atlantic coast of Europe. It forms the basis of a valuable commercial fishery and its ubiquity means that it plays a key role in coastal ecosystems and food webs. Like other filter feeding bivalves it can accumulate potent phytotoxins, to which it has evolved some immunity. The molecular origins of this immunity are of interest to evolutionary biologists, pharmaceutical companies and fisheries management. FindingsHere we report the genome sequencing of this species, conducted as part of the Wellcome Sanger 25 Genomes Project. This genome was assembled from PacBio reads and scaffolded with 10x Chromium and Hi-C data, and its 3,983 scaffolds have an N50 of 44.8 Mb (longest scaffold 60.1 Mb), with 92% of the assembly sequence contained in 19 scaffolds, corresponding to the 19 chromosomes found in this species. The total assembly spans 918.3 Mb, and is the best-scaffolded marine bivalve genome published to date, exhibiting 95.5% recovery of the metazoan BUSCO set. Gene annotation resulted in 67,741 gene models. Analysis of gene content revealed large numbers of gene duplicates, as previously seen in bivalves, with little gene loss, in comparison with the sequenced genomes of other marine bivalve species. ConclusionsThe genome assembly of Pecten maximus and its annotated gene set provide a high-quality platform for a wide range of investigations, including studies on such disparate topics as shell biomineralization, pigmentation, vision and resistance to algal toxins. As a result of our findings we highlight the sodium channel gene Nav1, known as a gene conferring resistance to saxitoxin and tetrodotoxin, as a candidate for further studies investigating immunity to domoic acid.

genomics↗

Low-intensity environmental education can enhance perceptions of culturally taboo wildlife

1.Traditional cultural beliefs influence perceptions of animals, and in some cases can result in persecution of wildlife. Stigmas against species associated with witchcraft, for example, can act as a barrier to the uptake of more cost effective, sustainable, and environmentally sound practices such as reducing crop damage by controlling rodent agricultural pests by relying on indigenous predators rather than pesticides. One way of enhancing perceptions of wildlife to increase participation in such ecologically-based rodent management (EBRM) schemes, is the development of environmental education initiatives. Low intensity programmes are cost-effective and can produce positive attitudinal shifts, but their impact has not been assessed for species strongly associated with witchcraft. We set out to test whether a single presentation on the natural history of owls (order Strigiformes) could improve perceptions of these species, and increase willingness to participate in an EBRM scheme that involved the installation of owl boxes to increase owl populations and reduce rodent populations and crop damage in agricultural fields. We used a questionnaire survey to assess perceptions of owls at four schools in two villages in South Africa. Our initial survey sampled perceptions of respondents before listening to the presentation. A follow-up survey conducted three months later sampled the perceptions of respondents that had listened to the presentation as well as perceptions of a control group that did not listen to the presentation. We found that associations between owls and witchcraft was a common theme driving negative perceptions of owls. Respondents that watched the presentation had more positive perceptions of owls than respondents that had not watched the presentation, and they were more likely to be willing to put up owl boxes near their home. Despite this shift, negative perceptions of owls still dominated responses due to cultural associations with the occult. These findings indicate that even low-intensity programmes can be effective at enhancing perceptions of wildlife associated with witchcraft. We suggest that environmental education programmes featuring culturally taboo species should adopt a culturally sensitive and locally tailored approach, focus on the benefits these species provide, and may be more effective when delivered with greater intensity.

scientific communication and education↗

High carnivore population density highlights the conservation value of industrialised sites

As the environment becomes increasingly altered by human development, the importance of understanding the ways in which wildlife interact with modified landscapes is becoming clear. Areas such as industrial sites are sometimes presumed to have little conservation value, but many of these sites have areas of less disturbed habitats around their core infrastructure, which could provide ideal conditions to support some species, such as mesocarnivores. We conducted the first assessments of the density of serval (Leptailurus serval) at the Secunda Synfuels Operations plant, South Africa. We ran three camera trap surveys to estimate serval density using a spatially explicit capture recapture framework. Servals occurred at densities of 76.20-101.21 animals per 100 km2, which are the highest recorded densities for this species, presumably due to high abundance of prey and the absence of persecution and/or competitor species. Our findings highlight the significant conservation potential of industrialised sites, and we suggest that such sites could help contribute towards meeting conservation goals.

ecology↗

Iran’s roads: mitigating the most serious threat to the critically endangered Asiatic cheetah Acinonyx jubatus venaticus

Wildlife-vehicle collisions are an important cause of mortality for many species, and the number of collisions is expected to grow rapidly as the global road network quickly expands over the next few decades. Wildlife-vehicle collisions also have the potential to be extremely detrimental to small wildlife populations, such as the critically endangered Asiatic cheetah (Acinonyx jubatus venaticus), with only 43 individuals remaining in the wild. We assessed the spatial distribution of road mortalities between 2004 and 2016 to identify roadkill hotspots involving Asiatic cheetahs in Iran using network kernel density estimation. A total of sixteen cheetah fatalities due to wildlife-vehicle collisions were recorded, and we identified six road fragments as roadkill hotspots. Efforts to reduce wildlife-cheetah collisions should be targeted in the densest hotspots. We review the options available to achieve this, and we recommend a strategic shift away from the ineffective warning signage currently used, and instead suggest adopting an evidence-based approach focusing on installing wildlife crossing structures in conjunction with fencing in roadkill hotspots. These measures will help to enhance the conservation status of the Asiatic cheetah, as the current high level of mortality of Asiatic cheetahs on Irans roads could have potentially dramatic impacts on this critically endangered subspecies.

ecology↗