Upper limb activity in myoelectric prosthesis users is biased towards the intact limb and appears unrelated to goal-directed task performance

Studies of the effectiveness of prosthetic hands involve assessing user performance on functional tasks in the lab/clinic, sometimes combined with self-report of real-world use. In this paper we compare real-world upper limb activity between a group of 20 myoelectric prosthesis users and 20 anatomically intact adults. Activity was measured from wrist-worn accelerometers over a 7-day period. The temporal patterns in upper limb activity are presented and the balance of activity between the two limbs quantified. We also evaluated the prosthesis users’ performance on a goal-directed task, characterised using measures including task success rate, completion time, gaze behaviour patterns, and kinematics (e.g. variability and patterns in hand aperture). Prosthesis users were heavily reliant on their intact limb during everyday life, in contrast to anatomically intact adults who demonstrated similar reliance on both upper limbs. There was no significant correlation between the amount of time a prosthesis was worn and reliance on the intact limb, and there was no significant correlation between either of these measures and any of the assessed kinematic and gaze-related measures of performance. We found participants who had been prescribed a prosthesis for longer to demonstrate more symmetry in their overall upper limb activity, although this was not reflected in the symmetry of unilateral limb use. With the exception of previously published case studies, this is the first report of real world upper limb activity in myoelectric prosthesis users and confirms the widely held belief that users are heavily reliant on their intact limb

Surface mediated cooperative interactions of drugs enhance mechanical forces for antibiotic action

The alarming increase of pathogenic bacteria that are resistant to multiple antibiotics is now recognized as a major health issue fuelling demand for new drugs. Bacterial resistance is often caused by molecular changes at the bacterial surface, which alter the nature of specific drug-target interactions. Here, we identify a novel mechanism by which drug-target interactions in resistant bacteria can be enhanced. We examined the surface forces generated by four antibiotics; vancomycin, ristomycin, chloroeremomycin and oritavancin against drug-susceptible and drug-resistant targets on a cantilever and demonstrated significant differences in mechanical response when drug-resistant targets are challenged with different antibiotics although no significant differences were observed when using susceptible targets. Remarkably, the binding affinity for oritavancin against drug-resistant targets (70 nM) was found to be 11,000 times stronger than for vancomycin (800 μM), a powerful antibiotic used as the last resort treatment for streptococcal and staphylococcal bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Using an exactly solvable model, which takes into account the solvent and membrane effects, we demonstrate that drug-target interactions are strengthened by pronounced polyvalent interactions catalyzed by the surface itself. These findings further enhance our understanding of antibiotic mode of action and will enable development of more effective therapies.We thank the EPSRC Interdisciplinary Research Centre in Nanotechnology (Cambridge, UCL, Bristol (GR/R45680/01), the EPSRC Grand Challenge in Nanotechnology for Healthcare (EP/G0620064/1), I-sense EPSRC IRC in Early Warning Sensing Systems for Infectious Diseases (EP/G062064/1), the EPSRC Speculative Engineering Program (EP/D50925/1), Royal Society (RS), Medicine Company Inc., USA, NHMRC Australia Fellowship (AF511105), UCL Graduate School Scholarship, UCL COMPLEX, Bio Nano Consulting (BNC), European Union FP7 Project VSMMART Nano (managed by BNC) and NHS Trusts Biomedical Research Centre (BRC) for funding

High intensity intermittent games-based activity and adolescents’ cognition: moderating effect of physical fitness

Background: An acute bout of exercise elicits a beneficial effect on subsequent cognitive function in adolescents. The effect of games-based activity, an ecologically valid and attractive exercise model for young people, remains unknown; as does the moderating effect of fitness on the acute exercise-cognition relationship. Therefore, the aim of the present study was to examine the effect of games-based activity on subsequent cognition in adolescents, and the moderating effect of fitness on this relationship. Methods: Following ethical approval, 39 adolescents (12.3 ± 0.7 year) completed an exercise and resting trial in a counterbalanced, randomised crossover design. During familiarisation, participants completed a multi-stage fitness test to predict VO2 peak. The exercise trial consisted of 60-min games-based activity (basketball), during which heart rate was 158 ± 11 beats∙min−1. A battery of cognitive function tests (Stroop test, Sternberg paradigm, trail making and d2 tests) were completed 30-min before, immediately following and 45-min following the basketball. Results: Response times on the complex level of the Stroop test were enhanced both immediately (p = 0.021) and 45-min (p = 0.035) post-exercise, and response times on the five item level of the Sternberg paradigm were enhanced immediately post-exercise (p = 0.023). There were no effects on the time taken to complete the trail making test or any outcome of the d2 test. In particular, response times were enhanced in the fitter adolescents 45-min post-exercise on both levels of the Stroop test (simple, p = 0.005; complex, p = 0.040) and on the three item level of the Sternberg paradigm immediately (p = 0.017) and 45-min (p = 0.008) post-exercise. Conclusions: Games-based activity enhanced executive function and working memory scanning speed in adolescents, an effect particularly evident in fitter adolescents, whilst the high intensity intermittent nature of games-based activity may be too demanding for less fit children

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Water from abandoned mines as a heat source: practical experiences of open- and closed-loop strategies, United Kingdom

Pilot heat pump systems have been installed at two former collieries in Yorkshire/Derbyshire, England, to extract heat from mine water. The installations represent three fundamental configurations of heat exchanger. At Caphouse Colliery, mine water is pumped through a heat exchanger coupled to a heat pump and then discharged to waste (an open-loop heat exchange system). The system performs with high thermal efficiency, but the drawbacks are: (1) it can only be operated when mine water is being actively pumped from the colliery shaft for the purposes of regional water-level management, and (2) the fact that the water is partially oxygenated means that iron oxyhydroxide precipitation occurs, necessitating regular removal of filters for cleaning. At Markham Colliery, near Bolsover, a small amount of mine water is pumped from depth in a flooded shaft, circulated through a heat exchanger coupled to a heat pump and then returned to the same mine shaft at a slightly different depth (a standing column arrangement). This system’s fundamental thermal efficiency is negatively impacted by the electrical power required to run the shaft submersible pump, but clogging issues are not significant. In the third system, at Caphouse, a heat exchanger is submerged in a mine water treatment pond (a closed-loop system). This can be run at any time, irrespective of mine pumping regime, and being a closed-loop system, is not susceptible to clogging issues

Access and utilisation of maternity care for disabled women who experience domestic abuse:a systematic review

BACKGROUND: Although disabled women are significantly more likely to experience domestic abuse during pregnancy than non-disabled women, very little is known about how maternity care access and utilisation is affected by the co-existence of disability and domestic abuse. This systematic review of the literature explored how domestic abuse impacts upon disabled women’s access to maternity services. METHODS: Eleven articles were identified through a search of six electronic databases and data were analysed to identify: the factors that facilitate or compromise access to care; the consequences of inadequate care for pregnant women’s health and wellbeing; and the effectiveness of existing strategies for improvement. RESULTS: Findings indicate that a mental health diagnosis, poor relationships with health professionals and environmental barriers can compromise women’s utilisation of maternity services. Domestic abuse can both compromise, and catalyse, access to services and social support is a positive factor when accessing care. Delayed and inadequate care has adverse effects on women’s physical and psychological health, however further research is required to fully explore the nature and extent of these consequences. Only one study identified strategies currently being used to improve access to services for disabled women experiencing abuse. CONCLUSIONS: Based upon the barriers and facilitators identified within the review, we suggest that future strategies for improvement should focus on: understanding women’s reasons for accessing care; fostering positive relationships; being women-centred; promoting environmental accessibility; and improving the strength of the evidence base

Restoring Akt1 activity in outgrowth endothelial cells from south asian men rescues vascular reparative potential

Recent data suggest reduced indices of vascular repair in South Asian men, a group at increased risk of cardiovascular events. Outgrowth endothelial cells (OEC) represent an attractive tool to study vascular repair in humans and may offer potential in cell-based repair therapies. We aimed to define and manipulate potential mechanisms of impaired vascular repair in South Asian (SA) men. In vitro and in vivo assays of vascular repair and angiogenesis were performed using OEC derived from SA men and matched European controls, prior defining potentially causal molecular mechanisms. SA OEC exhibited impaired colony formation, migration, and in vitro angiogenesis, associated with decreased expression of the proangiogenic molecules Akt1 and endothelial nitric oxide synthase (eNOS). Transfusion of European OEC into immunodeficient mice after wire-induced femoral artery injury augmented reendothelialization, in contrast with SA OEC and vehicle; SA OEC also failed to promote angiogenesis after induction of hind limb ischemia. Expression of constitutively active Akt1 (E17KAkt), but not green fluorescent protein control, in SA OEC increased in vitro angiogenesis, which was abrogated by a NOS antagonist. Moreover, E17KAkt expressing SA OEC promoted re-endothelialization of wire-injured femoral arteries, and perfusion recovery of ischemic limbs, to a magnitude comparable with nonmanipulated European OEC. Silencing Akt1 in European OEC recapitulated the functional deficits noted in SA OEC. Reduced signaling via the Akt/eNOS axis is causally linked with impaired OEC-mediated vascular repair in South Asian men. These data prove the principle of rescuing marked reparative dysfunction in OEC derived from these men.This work was supported by the British Heart Foundation, London, UK, and the Diabetes Research and Wellness Foundation, Portsmouth, UK

Investigating Agrobacterium-Mediated Transformation of Verticillium albo-atrum on Plant Surfaces

Background: Agrobacterium tumefaciens has long been known to transform plant tissue in nature as part of its infection process. This natural mechanism has been utilised over the last few decades in laboratories world wide to genetically manipulate many species of plants. More recently this technology has been successfully applied to non-plant organisms in the laboratory, including fungi, where the plant wound hormone acetosyringone, an inducer of transformation, is supplied exogenously. In the natural environment it is possible that Agrobacterium and fungi may encounter each other at plant wound sites, where acetosyringone would be present, raising the possibility of natural gene transfer from bacterium to fungus. Methodology/Principal Findings: We investigate this hypothesis through the development of experiments designed to replicate such a situation at a plant wound site. A. tumefaciens harbouring the plasmid pCAMDsRed was co-cultivated with the common plant pathogenic fungus Verticillium albo-atrum on a range of wounded plant tissues. Fungal transformants were obtained from co-cultivation on a range of plant tissue types, demonstrating that plant tissue provides sufficient vir gene inducers to allow A. tumefaciens to transform fungi in planta. Conclusions/Significance: This work raises interesting questions about whether A. tumefaciens may be able to transform organisms other than plants in nature, or indeed should be considered during GM risk assessments, with furthe