Understanding adaptive gait in lower-limb amputees: insights from multivariate analyses.

BACKGROUND: In this paper we use multivariate statistical techniques to gain insights into how adaptive gait involving obstacle crossing is regulated in lower-limb amputees compared to able-bodied controls, with the aim of identifying underlying characteristics that differ between the two groups and consequently highlighting gait deficits in the amputees. METHODS: Eight unilateral trans-tibial amputees and twelve able-bodied controls completed adaptive gait trials involving negotiating various height obstacles; with amputees leading with their prosthetic limb. Spatiotemporal variables that are regularly used to quantify how gait is adapted when crossing obstacles were determined and subsequently analysed using multivariate statistical techniques. RESULTS AND DISCUSSION: There were fundamental differences in the adaptive gait between the two groups. Compared to controls, amputees had a reduced approach velocity, reduced foot placement distance before and after the obstacle and reduced foot clearance over it, and reduced lead-limb knee flexion during the step following crossing. Logistic regression analysis highlighted the variables that best distinguished between the gait of the two groups and multiple regression analysis (with approach velocity as a controlling factor) helped identify what gait adaptations were driving the differences seen in these variables. Getting closer to the obstacle before crossing it appeared to be a strategy to ensure the heel of the lead-limb foot passed over the obstacle prior to the foot being lowered to the ground. Despite adopting such a heel clearance strategy, the lead-foot was positioned closer to the obstacle following crossing, which was likely a result of a desire to attain a limb/foot angle and orientation at instant of landing that minimised loads on the residuum (as evidenced by the reduced lead-limb knee flexion during the step following crossing). These changes in foot placement meant the foot was in a different part of swing at point of crossing and this explains why foot clearance was considerably reduced in amputees. CONCLUSIONS: These results highlight that trans-tibial amputees use quite different gait adaptations to cross obstacles compared with controls (at least when leading with their prosthetic limb), indicating they are governed by different constraints; seemingly related to how they land on/load their prosthesis after crossing the obstacle

Which prosthetic foot to prescribe?

Introduction: Clinicians typically use findings from cohort studies to objectively inform judgements regarding the potential (dis)advantages of prescribing a new prosthetic device. However, before finalising prescription a clinician will typically ask a patient to 'try out' a change of prosthetic device while the patient is at the clinic. Observed differences in gait when using the new device should be the result of the device’s mechanical function, but could also conceivably be due to patient related factors which can change from day-to-day and can thus make device comparisons unreliable. To determine whether a device’s mechanical function consistently has a more meaningful impact on gait than patient-related factors, the present study undertook quantitative gait analyses of a trans-tibial amputee walking using two different foot-ankle devices on two occasions over a year apart. If the observed differences present between devices, established using quantitative gait analysis, were in the same direction and of similar magnitude on each of the two occasions, this would indicate that device-related factors were more important than patient-related factors. Methods: One adult male with a unilateral trans-tibial amputation completed repeated walking trials using two different prosthetic foot devices on two separate occasions, 14 months apart. Walking speed and sagittal plane joint kinematics and kinetics for both limbs were assessed on each occasion. Clinically meaningful differences in these biomechanical outcome variables were defined as those with an effect size difference (d) between prosthetic conditions of at least 0.4 (i.e. 'medium' effect size). Results: Eight variables namely, walking speed, prosthetic 'ankle' peak plantar- and dorsi-flexion and peak positive power, and residual knee loading response flexion, peak stance-phase extension and flexion moments and peak negative power, displayed clinically meaningful differences (d > 0.4) between foot devices during the first session. All eight of these showed similar effect size differences during the second session despite the participant being heavier and older. Conclusions: Findings suggest that a prosthetic device's mechanical function consistently has a more meaningful impact on gait than patient-related factors. These findings support the current clinical practice of making decisions regarding prosthetic prescription for an individual, based on a single session evaluation of their gait using two different devices. However, to confirm this conclusion, a case series using the same approach as the present study could be undertaken

Synovial cell metabolism and chronic inflammation in rheumatoid arthritis

Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principle site of inflammation in RA. Here the resident cells are the fibroblast-like synoviocytes (FLS) and the synovial tissue macrophages (STM), which are transformed toward overproduction of enzymes which degrade cartilage and bone, and cytokines which promote immune cell infiltration. Recent studies have shown metabolic changes in both FLS and macrophages from RA patients and these may be therapeutically targetable. However, as the origins and subset specific functions of synoviocytes are poorly understood and the signaling modules which control metabolic deviation in RA synovial cells are yet to be explored, significant additional research is needed to translate these findings toward clinical application. Furthermore, in many inflamed tissues, different cell types can forge metabolic collaborations through solute carriers (SLC) in their membranes, to meet a high demand for energy or biomolecules. Such relationships are likely to exist in the synovium and are yet to be explored. Finally, it is not yet known whether metabolic change is a consequence of disease or if primary changes to cellular metabolism might underlie or contribute to early stage disease pathogenesis. This article collates what is known about metabolism in synovial tissue cells and highlights future research directions in this area

Spring-mass behavioural adaptations to acute changes in prosthetic blade stiffness during submaximal running in unilateral transtibial prosthesis users

Background: Individuals with lower-limb amputation can use running specific prostheses (RSP) that store and then return elastic energy during stance. However, it is unclear whether varying the stiffness category of the same RSP affects spring-mass behaviour during self-selected, submaximal speed running in individuals with unilateral transtibial amputation. Research question: The current study investigates how varying RSP stiffness affects limb stiffness, running performance, and associated joint kinetics in individuals with a unilateral transtibial amputation. Methods: Kinematic and ground reaction force data were collected from eight males with unilateral transtibial amputation who ran at self-selected submaximal speeds along a 15 m runway in three RSP stiffness conditions; recommended habitual stiffness (HAB) and, following 10-minutes of familiarisation, stiffness categories above (+1) and below (-1) the HAB. Stance-phase centre of mass velocity, contact time, limb stiffness’ and joint/RSP work were computed for each limb across RSP stiffness conditions. Results: With increased RSP stiffness, prosthetic limb stiffness increased, whilst intact limb stiffness decreased slightly (p<0.03). Centre of mass forward velocity during stance-phase (p<0.02) and contact time (p<0.04) were higher in the intact limb and lower in the prosthetic limb but were unaffected by RSP stiffness. Intact limb hip joint positive work increased for both the +1 and -1 conditions but remained unchanged across conditions in the prosthetic limb (p<0.02). Significance: In response to changes in RSP stiffness, there were acute increased mechanical demands on the intact limb, reflecting a reliance on the intact limb during running. However, overall running speed was unaffected, suggesting participants acutely adapted to an RSP of a non-prescribed stiffness

Fano 3-folds in P2xP2 format, Tom and Jerry

We study Q-factorial terminal Fano 3-folds whose equations are modelled on those of the Segre embedding of P^2xP^2. These lie in codimension 4 in their total anticanonical embedding and have Picard rank 2. They fit into the current state of classification in three different ways. Some families arise as unprojections of degenerations of complete intersections, where the generic unprojection is a known prime Fano 3-fold in codimension 3; these are new, and an analysis of their Gorenstein projections reveals yet other new families. Others represent the "second Tom" unprojection families already known in codimension 4, and we show that every such family contains one of our models. Yet others have no easy Gorenstein projection analysis at all, so prove the existence of Fano components on their Hilbert scheme

Preserving Madagascar's Natural Heritage: The Importance of Keeping the Island's Vertebrate Fossils in the Public Domain

No Abstrac

LHC Searches for Non-Chiral Weakly Charged Multiplets

Because the TeV-scale to be probed at the Large Hadron Collider should shed light on the naturalness, hierarchy, and dark matter problems, most searches to date have focused on new physics signatures motivated by possible solutions to these puzzles. In this paper, we consider some candidates for new states that although not well-motivated from this standpoint are obvious possibilities that current search strategies would miss. In particular we consider vector representations of fermions in multiplets of $SU(2)_L$ with a lightest neutral state. Standard search strategies would fail to find such particles because of the expected small one-loop-level splitting between charged and neutral states.Comment: 16 pages, 9 figure

Insights into electrosensory organ development, physiology and evolution from a lateral line-enriched transcriptome

The anamniote lateral line system, comprising mechanosensory neuromasts and electrosensory ampullary organs, is a useful model for investigating the developmental and evolutionary diversification of different organs and cell types. Zebrafish neuromast development is increasingly well understood, but neither zebrafish nor $\textit{Xenopus}$ is electroreceptive and our molecular understanding of ampullary organ development is rudimentary. We have used RNA-seq to generate a lateral line-enriched gene-set from late-larval paddlefish ($\textit{Polyodon spathula}$). Validation of a subset reveals expression in developing ampullary organs of transcription factor genes critical for hair cell development, and genes essential for glutamate release at hair cell ribbon synapses, suggesting close developmental, physiological and evolutionary links between non-teleost electroreceptors and hair cells. We identify an ampullary organ-specific proneural transcription factor, and candidates for the voltage-sensing L-type Ca$_v$ channel and rectifying K$_v$ channel predicted from skate (cartilaginous fish) ampullary organ electrophysiology. Overall, our results illuminate ampullary organ development, physiology and evolution.Biotechnology and Biological Sciences Research Council (BB/F00818X/1), Leverhulme Trust (RPG-383), Fisheries Society of the British Isles (Research Grant), National Science Foundation (IOS 1557857, IOS 1144965

Breast imaging technology: Application of magnetic resonance imaging to angiogenesis in breast cancer

Magnetic resonance imaging (MRI) techniques enable vascular function to be mapped with high spatial resolution. Current methods for imaging in breast cancer are described, and a review of recent studies that compared dynamic contrast-enhanced MRI with histopathological indicators of tumour vascular status is provided. These studies show correlation between in vivo dynamic contrast measurements and in vitro histopathology. Dynamic contrast enhanced MRI is also being applied to assessment of the response of breast tumours to treatment

The effects of walking speed on minimum toe clearance and on the temporal relationship between minimum clearance and peak swing-foot velocity in unilateral trans-tibial amputees

yesBackground: Minimum toe clearance is a critical gait event because it coincides with peak forward velocity of the swing foot, and thus, there is an increased risk of tripping and falling. Trans-tibial amputees have increased risk of tripping compared to able-bodied individuals. Assessment of toe clearance during gait is thus clinically relevant. In able-bodied gait, minimum toe clearance increases with faster walking speeds, and it is widely reported that there is synchronicity between when peak swing-foot velocity and minimum toe clearance occur. There are no such studies involving lower-limb amputees. Objectives: To determine the effects of walking speed on minimum toe clearance and on the temporal relationship between clearance and peak swing-foot velocity in unilateral trans-tibial amputees. Study design: Cross-sectional. Methods: A total of 10 trans-tibial participants walked at slow, customary and fast speeds. Minimum toe clearance and the timings of minimum toe clearance and peak swing-foot velocity were determined and compared between intact and prosthetic sides. Results: Minimum toe clearance was reduced on the prosthetic side and, unlike on the intact side, did not increase with walking speed increase. Peak swing-foot velocity consistently occurred (~0.014 s) after point of minimum toe clearance on both limbs across all walking speeds, but there was no significant difference in the toe–ground clearance between the two events. Conclusion: The absence of speed related increases in minimum toe clearance on the prosthetic side suggests that speed related modulation of toe clearance for an intact limb typically occurs at the swing-limb ankle. The temporal consistency between peak foot velocity and minimum toe clearance on each limb suggests that swing-phase inter-segmental coordination is unaffected by trans-tibial amputation. Clinical relevance The lack of increase in minimum toe clearance on the prosthetic side at higher walking speeds may potentially increase risk of tripping. Findings indicate that determining the instant of peak swing-foot velocity will also consistently identify when/where minimum toe clearance occurs