Muscle contributions to ballistic reaching kinematics in individuals with chronic stroke

Motor impairments such as abnormal muscle co-activation (flexion synergy) and hyperactive stretch reflexes (spasticity) are thought to greatly disrupt reaching function following stroke. In this investigation, the individual contributions of both are considered and the hypothesis tested is whether abnormal flexor co-activation is the dominant contributor to impaired reaching. In this study, participants made ballistic horizontal reaches on the admittance-controlled robot, the ACT3D. Reaches were performed while elevating the arm just above a horizontal haptic surface/plane at five different abduction loads standardized to increasing percentages of the participant’s maximum abduction strength. As a general effect, peak elbow angular velocity decreased significantly (p<0.05) as a function of abduction loading as one would expect should flexion synergy and/or spasticity be at play. We compared elbow muscle activation during time-windows anchored to the onset of ballistic reaching. EMG analysis indicated that at the onset of lifting the arm and maintaining a quasi-static starting position, elbow flexor activation increased (p<0.05) as a function of abduction loading illustrating the manifestation of flexion synergy. This flexor activity was countered by a concurrent increase (p<0.05) in extensor activation in order to maintain the quasi-static starting position. Following the onset of the reach, open loop (first 25ms) muscle activation was significant (p<0.05) for an ~12% increase in extensor activation that was attributed to initiation of the reach. Furthermore, closed loop (25ms to peak velocity) muscle activation was significant (p<0.05) for an ~20% increase in extensor activation that was attributed to intent to achieve maximum velocity. No additional flexor activation occurred during open or closed-loop time windows. In fact, synergistic flexor activation at the onset of lifting (15%) was nearly 4-fold and significantly greater (p<0.05) than the reflexive flexor activity (4%) in the closed loop portion of the reach indicating that reaching function is greatly more impacted by activation of the elbow flexors as part of flexion synergy than any subsequent increased activation of flexors due to stretch reflex. It should be acknowledged that the primary limitation of this work is the solely volitional nature of the reaching task that can introduce unavoidable performance variance. However, this work provides important justification for conducting future work that seeks to directly quantify stretch reflex contributions via velocity-controlled elbow perturbations under quasi-static abduction loading and dynamic reaching conditions

Assessing the influence of sea walls on the coastal vulnerability of a pinned, soft-cliff, sandy coastline

Coastal defences have long been employed to halt or slow coastal erosion. Their impact on local sediment flux and ecology has been studied in detail through field studies and numerical simulations. The non-local impact of a modified sediment flux regime on mesoscale erosion and accretion has received less attention. Morphological changes at this scale due to defended structures can be difficult to quantify or identify with field data. Engineering scale numerical models, often applied to assess the design of modern defences on local coastal erosion, tend not to cover large stretches of coast and are rarely applied to assess the impact of older structures. We extend previous work to explore the influences of sea walls on the evolution and morphological sensitivity of a pinned, soft-cliff, sandy coastline under a changing wave climate. The Holderness coast of East Yorkshire, UK, is used as a case study, represented both as a defended example with major sea walls included and a natural example where no sea defences exist. Using a mesoscale numerical coastal evolution model, stochastic wave climate data are perturbed gradually to assess the sensitivity of the coastal morphology to changing wave climate for both the defended and natural scenarios. Comparative analysis of the simulated output suggests that sea walls in the south of the region have a greater impact on sediment flux due to the increased sediment availability along this part of the coast. Multiple defended structures, including those separated by several kilometres, were found to interact with each other, producing a complex imprint on coastal morphology under a changing wave climate. Although spatially and temporally heterogeneous, sea walls generally slowed coastal recession and accumulated sediment on their up-drift side

Coastal vulnerability of a pinned, soft-cliff coastline. Part II, assessing the influence of sea walls on future morphology

Coastal defences have long been employed to halt or slow coastal erosion, and their impact on local sediment flux and ecology has been studied in detail through field research and numerical simulation. The nonlocal impact of a modified sediment flux regime on mesoscale erosion and accretion has received less attention. Morphological changes at this scale due to defending structures can be difficult to quantify or identify with field data. Engineering-scale numerical models, often applied to assess the design of modern defences on local coastal erosion, tend not to cover large stretches of coast and are rarely applied to assess the impact of older structures. We extend previous work to explore the influences of sea walls on the evolution and morphological sensitivity of a pinned, soft-cliff, sandy coastline under a changing wave climate. The Holderness coast of East Yorkshire, UK, is used as a case study to explore model scenarios where the coast is both defended with major sea walls and allowed to evolve naturally were there are no sea defences. Using a mesoscale numerical coastal evolution model, observed wave-climate data are perturbed linearly to assess the sensitivity of the coastal morphology to changing wave climate for both the defended and undefended scenarios. Comparative analysis of the simulated output suggests that sea walls in the south of the region have a greater impact on sediment flux due to increased sediment availability along this part of the coast. Multiple defence structures, including those separated by several kilometres, were found to interact with each other, producing complex changes in coastal morphology under a changing wave climate. Although spatially and temporally heterogeneous, sea walls generally slowed coastal recession and accumulated sediment on their up-drift side

An isotope dilution model for partitioning of phenylalanine and tyrosine uptake by the liver of lactating dairy cows

An isotope dilution model to describe the partitioning of phenylalanine (PHE) and tyrosine (TYR) in the bovine liver was developed. The model comprises four intracellular and six extracellular pools and various flows connecting these pools and external blood. Conservation of mass principles were applied to generate the fundamental equations describing the behaviour of the system in the steady state. The model was applied to datasets from multi-catheterised dairy cattle during a constant infusion of [1-13C] phenylalanine and [2,3,5,6-2H] tyrosine tracers. Model solutions described the extraction of PHE and TYR from the liver via the portal vein and hepatic artery. In addition, the exchange of free PHE and TYR between extracellular and intracellular pools was explained and the hydroxylation of PHE to TYR was estimated. The model was effective in providing information about the fates of PHE and TYR in the liver and could be used as part of a more complex system describing amino acid metabolism in the whole animal

Models based on the Mitscherlich equation for describing typical and atypical gas production profiles obtained from in vitro digestibility studies using equine faecal inoculum

Two models are proposed to describe atypical biphasic gas production profiles obtained from in vitro digestibility studies. The models are extensions of the standard Mitscherlich equation, comprising either two Mitscherlich terms or one Mitscherlich and one linear term. Two models that describe typical monophasic gas production curves, the standard Mitscherlich and the France model [a generalised Mitscherlich (root-t) equation], were assessed for comparison. Models were fitted to 25 gas production profiles resulting from incubating feedstuffs with faecal inocula from equines. Seventeen profiles displayed atypical biphasic patterns while the other eight displayed typical monophasic patterns. Models were evaluated using statistical measures of goodness-of-fit and by analysis of residuals. Good agreement was found between observed atypical profiles values and fitted values obtained with the two biphasic models, and both can revert to a simple Mitscherlich allowing them to describe typical monophasic profiles. The models contain kinetic fermentation parameters that can be used in conjunction with substrate degradability information and digesta passage rate to calculate extent of substrate degradation in the rumen or hindgut. Thus, models link the in vitro gas production technique to nutrient supply in the animal by providing information relating to digestion and nutritive value of feedstuffs

Equine nutrition: a survey of perceptions and practices of horse owners undertaking a massive open online course in equine nutrition

An online survey was designed to ascertain the following information: demographics, current feeding practices, and perceptions and knowledge of equine nutrition, including nutrition-related disorders. Response rate was 34% (6,538 respondents). More than 80% of respondents were horse owners or caretakers, with the majority owning between one and five horses (75%) aged 5 years and older (74%). Most kept their horses for pleasure (54%), with 33% using them mostly for competition and 13% using them for an equal mix of both pleasure and competition. Concentrates were fed by the majority (87%), and more than 70% stated that their horses had some access to pasture. Over half of respondents (60%) regularly monitored their horses' weight, with most doing this monthly. Weight tapes were most commonly used (62%), although many reported to guess the weight of their horse(s) with very few (5%) using weight scales. Under half (46%) stated that they regularly used body condition scoring (BCS), many did not use BCS at all (24%), and some did not know what BCS was (10%). Of those that did use BCS, most (36%) did this monthly, with others weekly (25%), daily (14%), and when they remembered (15%). Overall knowledge of nutrition was reported by most as average (median, 3 on Likert scale—average); however, respondents were less knowledgeable on the management of nutrition-related disorders

An illustrative analysis of atypical gas production profiles obtained from in vitro digestibility studies using fecal inoculum

14 páginas, 2 tablas, 6 figuras.Gas production profiles typically show a monotonically increasing monophasic pattern. However, atypical gas production profiles exist whereby at least two consecutive phases of gas production or additional extraneous features that distort the typical profile are present. Such profiles are more likely to occur with the use of a fecal inoculum and are much less well described. The presence of multiple phases or non-descript extraneous features makes it difficult to apply directly recommended modeling approaches such as standard response functions or classical growth functions. To overcome such difficulties, extensions of the Mitscherlich equation and a numerical modeling option also based on the Mitscherlich are explored. The numerical modeling option uses an estimate of relative rate obtained from the smoothed data profile and an estimate of maximum gas produced together with any lag time information drawn from the raw data to construct a simple Mitscherlich equation. In summary, this article illustrates the analysis of atypical gas production profiles obtained using a fecal inoculum and explores the methodology of numerical modeling to reconstruct equivalent typical growth-like trends.This research was funded in part by The Canada Research Chairs program, grant number 045867 (Natural Sciences and Engineering Research Council of Canada, Ottawa)

Modelling coastal erosion and sediment transport on the Dungeness Foreland, UK

Ageing coastal defence across the UK is challenging managers to redesign schemes to be resilient, cost-effective and have minimal or beneficial environmental impact. We take Dungeness and Romney Marsh, a region of high value in terms of habitat and energy infrastructure, as a case study that could potentially be a site for a ‘sandscaping’ project, i.e. an innovative, large-scale beach recharge scheme. At present, this location has both modified gravel barrier defences and engineered structures. We present results for a feasibility study to improve understanding of how ‘working with natural processes’ to manage coastal flood and erosion risk could provide and support defences protecting this site, ensuring an energy supply that is resilient to climate change. This modelling study investigates the impact of re-engineering the coastline with a series of sandscaping options that mimic the natural shape and former evolution of the Dungeness coastline. Particle tracking is used to show the potential pathways of recharged sediment (fine and medium sand) movement along the coastline in both calm and stormy conditions. A coastal evolution model is also applied to assess the alongshore impact of different intervention designs. It is found that the main sediment drift is likely to be towards the north along the coast and that considering larger interventions could possibly provide increased protection for up to 100 years. Further, a series of three smaller sandscaping interventions offers the greatest immediate reduction in erosion rate. The natural drift within the system causes the initial peninsula-shaped intervention to form a recurve that could potentially create additional areas supporting essential natural habitat within the area

Biomarker-guided sequential targeted therapies to overcome therapy resistance in rapidly evolving highly aggressive mammary tumors

Combinatorial targeted therapies are more effective in treating cancer by blocking by-pass mechanisms or inducing synthetic lethality. However, their clinical application is hampered by resistance and toxicity. To meet this important challenge, we developed and tested a novel concept of biomarker-guided sequential applications of various targeted therapies using ErbB2-overexpressing/PTEN-low, highly aggressive breast cancer as our model. Strikingly, sustained activation of ErbB2 and downstream pathways drives trastuzumab resistance in both PTEN-low/trastuzumab-resistant breast cancers from patients and mammary tumors with intratumoral heterogeneity from genetically-engineered mice. Although lapatinib initially inhibited trastuzumab-resistant mouse tumors, tumors by-passed the inhibition by activating the PI3K/mTOR signaling network as shown by the quantitative protein arrays. Interestingly, activation of the mTOR pathway was also observed in neoadjuvant lapatinib-treated patients manifesting lapatinib resistance. Trastuzumab + lapatinib resistance was effectively overcome by sequential application of a PI3K/mTOR dual kinase inhibitor (BEZ235) with no significant toxicity. However, our p-RTK array analysis demonstrated that BEZ235 treatment led to increased ErbB2 expression and phosphorylation in genetically-engineered mouse tumors and in 3-D, but not 2-D, culture, leading to BEZ235 resistance. Mechanistically, we identified ErbB2 protein stabilization and activation as a novel mechanism of BEZ235 resistance, which was reversed by subsequent treatment with lapatinib + BEZ235 combination. Remarkably, this sequential application of targeted therapies guided by biomarker changes in the tumors rapidly evolving resistance doubled the life-span of mice bearing exceedingly aggressive tumors. This fundamentally novel approach of using targeted therapies in a sequential order can effectively target and reprogram the signaling networks in cancers evolving resistance during treatment. © 2014 IBCB, SIBS, CAS All rights reserved