The biomechanics of the locust ovipositor valves : a unique digging apparatus

The female locust has a unique mechanism for digging in order to deposit its eggs deep in the ground. It utilizes two pairs of sclerotized valves to displace the granular matter, while extending its abdomen as it propagates underground. This ensures optimal conditions for the eggs to incubate, and provides them with protection from predators. Here, two major axes of operation of the digging valves are identified, one in parallel to the propagation direction of the ovipositor, and one perpendicular to it. The direction-dependent biomechanics of the locust major, dorsal digging valves are quantified and analyzed, under forces in the physiological range and beyond, considering hydration level, as well as the females’ age, or sexual maturation state. Our findings reveal that the responses of the valves to compression forces in the specific directions change upon sexual maturation to follow their function, and depend on environmental conditions. Namely, in the physiological force range, the valves are resistant to mechanical failure. In addition, mature females, which lay eggs, have stiffer valves, up to roughly nineteen times the stiffness of the pre-mature locusts. The valves are stiffer in the major working direction, corresponding to soil shuffling and compression, compared to the direction of propagation. Hydration of the valves reduces their stiffness but increases their resilience against failure. These findings provide mechanical and materials guidelines for the design of novel non-drilling excavating tools, including 3D-printed anisotropic materials based on composites.Statement of significance The female locust lay its eggs underground in order to protect them from predators and to provide them with optimal conditions for hatching. In order to dig into the ground, it uses two pairs of valves: The ventral pair is plugged as a wedge, while the dorsal pair performs the digging of the oviposition tunnel. We study the mechanical response of the digging valves, depending on age, hydration level and direction of operation. Our findings show that during the course of roughly two weeks in the life of the adult female, the digging valves become up to nineteen-fold stiffer against failure, in order to fulfill their function as diggers. While hydration reduces the stiffness, it also increases the resilience against failure and renders the valves unbreakable within the estimated physiological force range and beyond. The digging valves are consistently stiffer in the digging direction than in the perpendicular direction, implying on their form-follows-function design.Competing Interest StatementThe authors have declared no competing interest

Systems Science and Health: Using Analytical Approaches to Evaluate Healthcare Policy Decisions

This collection of presentations is from the mini-symposium entitled Systems Science and Health: Using Analytical Approaches to Evaluate Healthcare Policy Decisions. The focus of this symposium is on systems science applications to health research. Systems science is a collection of analytical computer simulation techniques which are used to evaluate optimize and improve healthcare delivery processes. These techniques account for the complexity of the healthcare system and healthcare processes by modeling nonlinear relationships between variables, the feedback effects, delays and soft variables. The analysis stresses heterogeneity of agents, resistance to change, potential unintended consequences, and behavioral emergence in complex systems. Such models use historical data to simulate the operations of healthcare systems providing an approximation of future outcomes. The presenters will discuss several different types of simulations methods, highlight recent advances, and describe funding opportunities from the National Institutes of Health. Examples from chronic disease patient chains, physician incentive redesign, clinic staffing and Emergency Department redesign will be discussed

Achilles tendon moment arm length is smaller in children with cerebral palsy than in typically developing children

When studying muscle and whole-body function in children with cerebral palsy (CP), knowledge about both internal and external moment arms is essential since they determine the mechanical advantage of a muscle over an external force. Here we asked if Achilles tendon moment arm (MAAT) length is different in children with CP and age-matched typically developing (TD) children, and if MAAT can be predicted from anthropometric measurements. Sixteen children with CP (age: 10y 7 m ± 3y, 7 hemiplegia, 12 diplegia, GMFCS level: I (11) and II (8)) and twenty TD children (age: 10y 6 m ± 3y) participated in this case-control study. MAAT was calculated at 20° plantarflexion by differentiating calcaneus displacement with respect to ankle angle. Seven anthropometric variables were measured and related to MAAT. We found normalized MAAT to be 15% (∼7 mm) smaller in children with CP compared to TD children (p = 0.003). MAAT could be predicted by all anthropometric measurements with tibia length explaining 79% and 72% of variance in children with CP and TD children, respectively. Our findings have important implications for clinical decision making since MAAT influences the mechanical advantage about the ankle, which contributes to movement function and is manipulated surgically

Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells

CD4-based decoy approaches against HIV-1 are attractive options for long-term viral control, but initial designs, including soluble CD4 (sCD4) and CD4-Ig, were ineffective. To evaluate a therapeutic that more accurately mimics HIV-1 target cells compared with monomeric sCD4 and dimeric CD4-Ig, we generated virus-like nanoparticles that present clusters of membrane-associated CD4 (CD4-VLPs) to permit high-avidity binding of trimeric HIV-1 envelope spikes. In neutralization assays, CD4-VLPs were >12,000-fold more potent than sCD4 and CD4-Ig and >100-fold more potent than the broadly neutralizing antibody (bNAb) 3BNC117, with >12,000-fold improvements against strains poorly neutralized by 3BNC117. CD4-VLPs also neutralized patient-derived viral isolates that were resistant to 3BNC117 and other bNAbs. Intraperitoneal injections of CD4-CCR5-VLP produced only subneutralizing plasma concentrations in HIV-1–infected humanized mice but elicited CD4-binding site mutations that reduced viral fitness. All mutant viruses showed reduced sensitivity to sCD4 and CD4-Ig but remained sensitive to neutralization by CD4-VLPs in vitro. In vitro evolution studies demonstrated that CD4-VLPs effectively controlled HIV-1 replication at neutralizing concentrations, and viral escape was not observed. Moreover, CD4-VLPs potently neutralized viral swarms that were completely resistant to CD4-Ig, suggesting that escape pathways that confer resistance against conventional CD4-based inhibitors are ineffective against CD4-VLPs. These findings suggest that therapeutics that mimic HIV-1 target cells could prevent viral escape by exposing a universal vulnerability of HIV-1: the requirement to bind CD4 on a target cell. We propose that therapeutic and delivery strategies that ensure durable bioavailability need to be developed to translate this concept into a clinically feasible functional cure therapy

Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells

CD4-based decoy approaches against HIV-1 are attractive options for long-term viral control, but initial designs, including soluble CD4 (sCD4) and CD4-Ig, were ineffective. To evaluate a therapeutic that more accurately mimics HIV-1 target cells compared with monomeric sCD4 and dimeric CD4-Ig, we generated virus-like nanoparticles that present clusters of membrane-associated CD4 (CD4-VLPs) to permit high-avidity binding of trimeric HIV-1 envelope spikes. In neutralization assays, CD4-VLPs were >12,000-fold more potent than sCD4 and CD4-Ig and >100-fold more potent than the broadly neutralizing antibody (bNAb) 3BNC117, with >12,000-fold improvements against strains poorly neutralized by 3BNC117. CD4-VLPs also neutralized patient-derived viral isolates that were resistant to 3BNC117 and other bNAbs. Intraperitoneal injections of CD4-CCR5-VLP produced only subneutralizing plasma concentrations in HIV-1–infected humanized mice but elicited CD4-binding site mutations that reduced viral fitness. All mutant viruses showed reduced sensitivity to sCD4 and CD4-Ig but remained sensitive to neutralization by CD4-VLPs in vitro. In vitro evolution studies demonstrated that CD4-VLPs effectively controlled HIV-1 replication at neutralizing concentrations, and viral escape was not observed. Moreover, CD4-VLPs potently neutralized viral swarms that were completely resistant to CD4-Ig, suggesting that escape pathways that confer resistance against conventional CD4-based inhibitors are ineffective against CD4-VLPs. These findings suggest that therapeutics that mimic HIV-1 target cells could prevent viral escape by exposing a universal vulnerability of HIV-1: the requirement to bind CD4 on a target cell. We propose that therapeutic and delivery strategies that ensure durable bioavailability need to be developed to translate this concept into a clinically feasible functional cure therapy

Seasonality of Overseas Tourism Demand in Scotland: A Regional Analysis

This paper examines patterns of seasonality in international tourism to the regions of Scotland. Quarterly numbers of overnight stays are disaggregated by trip purpose. Seasonality in vacation tourism to Scotland is shown to be defined by more than a simple rural–urban division. Overseas visiting friends and relatives (VFR) tourism is largely an urban phenomenon and is consequently less seasonal than vacation tourism. Lower seasonal concentration of VFR tourism is not uniform across the regions. Although levels of seasonal intensity of business tourism to the three principal cities of Scotland are approximately the same, there are noticeable variations over time

Learning To Be Affected: Social suffering and total pain at life’s borders.

The practice of Live Sociology in situations of pain and suffering is the author’s focus. An outline of the challenges of understanding pain is followed by a discussion of Bourdieu’s ‘social suffering’ (1999) and the palliative care philosophy of ‘total pain’. Using examples from qualitative research on disadvantaged dying migrants in the UK, attention is given to the methods that are improvised by dying people and care practitioners in attempts to bridge intersubjective divides, where the causes and routes of pain can be ontologically and temporally indeterminate and/or withdrawn. The paper contends that these latter phenomena are the incitement for the inventive bridging and performative work of care and Live Sociological methods, both of which are concerned with opposing suffering. Drawing from the ontology of total pain, I highlight the importance of (i) an engagement with a range of materials out of which attempts at intersubjective bridging can be produced, and which exceed the social, the material, and the temporally linear; and (ii) an empirical sensibility that is hospitable to the inaccessible and non-relational

Medial gastrocnemius volume and echo-intensity after botulinum neurotoxin A interventions in children with spastic cerebral palsy.

AIM: This cross-sectional investigation evaluated whether recurrent botulinum neurotoxin A (BoNT-A) interventions to the medial gastrocnemius have an influence on muscle morphology, beyond Gross Motor Function Classification System (GMFCS) level. METHOD: A cohort of typically developing children (n=67; 43 males, 24 females; median age 9y 11mo [range 7y 10mo-11y 6mo]), a cohort of children with spastic cerebral palsy (CP) naive to BoNT-A interventions (No-BoNT-A; n=19; 10 males, nine females; median age 9y 3mo [range 8y 5mo-10y 10mo]) and a cohort of children with spastic CP with a minimum of three recurrent BoNT-A interventions to the medial gastrocnemius (BoNT-A; n=19; 13 males, six females; median age 9y 8mo [range 7y 3mo-10y 7mo]) were recruited. Three-dimensional freehand ultrasound was used to estimate medial gastrocnemius volume normalized to body mass and echo-intensity. RESULTS: Normalized medial gastrocnemius volume and echo-intensity significantly differed between the two spastic CP cohorts (p≤0.05), with the BoNT-A cohort having larger alterations. Associations between normalized medial gastrocnemius volume and echo-intensity were highest in the No-BoNT-A cohort, followed by the BoNT-A cohort. Multiple regression analyses revealed that both GMFCS level and BoNT-A intervention history were significantly associated with smaller normalized medial gastrocnemius volume and higher echo-intensity. INTERPRETATION: Recurrent BoNT-A interventions may induce alterations to medial gastrocnemius volume and echo-intensity beyond the natural history of the spastic CP pathology. WHAT THIS PAPER ADDS: In spastic cerebral palsy, medial gastrocnemius volumes are smaller and echo-intensities higher compared with typical development. Alterations after botulinum neurotoxin A intervention (BoNT-A) are larger than in no BoNT-A intervention. Gross Motor Function Classification System level and BoNT-A history significantly associate with medial gastrocnemius and echo-intensity alterations

Personalisation of Plantarflexor Musculotendon Model Parameters in Children with Cerebral Palsy.

Neuromusculoskeletal models can be used to evaluate aberrant muscle function in cerebral palsy (CP), for example by estimating muscle and joint contact forces during gait. However, to be accurate, models should include representative musculotendon parameters. We aimed to estimate personalised parameters that capture the mechanical behaviour of the plantarflexors in children with CP and typically developing (TD) children. Ankle angle (using motion capture), torque (using a load-cell), and medial gastrocnemius fascicle lengths (using ultrasound) were measured during slow passive ankle dorsiflexion rotation for thirteen children with spastic CP and thirteen TD children. Per subject, the measured rotation was input to a scaled OpenSim model to simulate the torque and fascicle length output. Musculotendon model parameters were personalised by the best match between simulated and experimental torque-angle and fascicle length-angle curves according to a least-squares fit. Personalised tendon slack lengths were significantly longer and optimal fibre lengths significantly shorter in CP than model defaults and than in TD. Personalised tendon compliance was substantially higher in both groups compared to the model default. The presented method to personalise musculotendon parameters will likely yield more accurate simulations of subject-specific muscle mechanics, to help us understand the effects of altered musculotendon properties in CP