A self-management programme to reduce falls and improve safe mobility in people with secondary progressive MS: the BRiMS feasibility RCT

This is the final version, also available from NIHR journals library via the DOI in this record.Abstract Background Balance, mobility impairments and falls are common problems for people with multiple sclerosis (MS). Our ongoing research has led to the development of Balance Right in MS (BRiMS), a 13-week home- and group-based exercise and education programme intended to improve balance and encourage safer mobility. Objective This feasibility trial aimed to obtain the necessary data and operational experience to finalise the planning of a future definitive multicentre randomised controlled trial. Design Randomised controlled feasibility trial. Participants were block randomised 1 : 1. Researcher-blinded assessments were scheduled at baseline and at 15 and 27 weeks post randomisation. As is appropriate in a feasibility trial, statistical analyses were descriptive rather than involving formal/inferential comparisons. The qualitative elements utilised template analysis as the chosen analytical framework. Setting Four sites across the UK. Participants Eligibility criteria included having a diagnosis of secondary progressive MS, an Expanded Disability Status Scale (EDSS) score of between ≥ 4.0 and ≤ 7.0 points and a self-report of two or more falls in the preceding 6 months. Interventions Intervention – manualised 13-week education and exercise programme (BRiMS) plus usual care. Comparator – usual care alone. Main outcome measures Trial feasibility, proposed outcomes for the definitive trial (including impact of MS, mobility, quality of life and falls), feasibility of the BRiMS programme (via process evaluation) and economic data. Results A total of 56 participants (mean age 59.7 years, standard deviation 9.7 years; 66% female; median EDSS score of 6.0 points, interquartile range 6.0–6.5 points) were recruited in 5 months; 30 were block randomised to the intervention group. The demographic and clinical data were broadly comparable at baseline; however, the intervention group scored worse on the majority of baseline outcome measures. Eleven participants (19.6%) withdrew or were lost to follow-up. Worsening of MS-related symptoms unrelated to the trial was the most common reason (n = 5) for withdrawal. Potential primary and secondary outcomes and economic data had completion rates of > 98% for all those assessed. However, the overall return rate for the patient-reported falls diary was 62%. After adjusting for baseline score, the differences between the groups (intervention compared with usual care) at week 27 for the potential primary outcomes were MS Walking Scale (12-item) version 2 –7.7 [95% confidence interval (CI) –17.2 to 1.8], MS Impact Scale (29-item) version 2 (MSIS-29vs2) physical 0.6 (95% CI –7.8 to 9) and MSIS-29vs2 psychological –0.4 (95% CI –9.9 to 9) (negative score indicates improvement). After the removal of one outlier, a total of 715 falls were self-reported over the 27-week trial period, with substantial variation between individuals (range 0–93 falls). Of these 715 falls, 101 (14%) were reported as injurious. Qualitative feedback indicated that trial processes and participant burden were acceptable, and participants highlighted physical and behavioural changes that they perceived to result from undertaking BRiMS. Engagement varied, influenced by a range of condition- and context-related factors. Suggestions to improve the utility and accessibility of BRiMS were highlighted. Conclusions The results suggest that the trial procedures are feasible and acceptable, and retention, programme engagement and outcome completion rates were sufficient to satisfy the a priori progression criteria. Challenges were experienced in some areas of data collection, such as completion of daily diaries.National Institute for Health Research (NIHR

Establishing connectivity between the existing networked music notation packages Quintet.net, Decibel ScorePlayer and MaxScore

In this paper we outline a collaboration where live internet-based and local collaboration between research groups/musicians from Decibel New Music Ensemble (Perth, Australia) and ZM (Hamburg, Germany), was facilitated by novel innovations in customised software solutions employed by both groups. The exchange was funded by the Deutscher Akademischer Austauschdienst and Universities Australia. Both groups were previously engaged in the research and performance of similar musical repertoire such as John Cage\u27s \u27Five\u27 (1988) and \u27Variations I — VIII\u27 (1958-67) among others, the performances of which utilise graphic, animated and extended traditional Western music notation. Preliminary steps were taken to achieve communication between the three existing network music notation packages, the Decibel ScorePlayer, MaxScore and quintet.net, facilitating a merging – and ultimately an extension – of notational approaches previously prescribed by each music notation package. In addition to the technical innovations required to achieve such a project, we consider the outcomes and future directions of the project, as well as their relevance for the wider contemporary music community

Mechanical Effects of Fine-Wire Climbing on the Hindlimb Skeleton of Mice

poster abstractHigh-impact exercise (running/jumping) can stimulate multiple anabolic responses (increased trabecular bone volume, BV/TV) in the skeleton, but is also linked to an increased incidence of skeletal fracture. Thus, it is not an appropriate treatment for patients with elevated fracture risks. However, multi-directional offaxis mechanical loading can also elicit anabolic responses, even when magnitudes are relatively low. This represents a potential alternative to high-impact exercise for improving skeletal mechanical properties. To test this hypothesis, we raised twelve weanling female C57BL/6 mice to 4 months of age in custom enclosures that prevent (control) or require (experimental) manual and pedal grasping while balancing and climbing above narrow wire substrates. At sacrifice, we measured whole mouse bone density (DEXA) and performed architectural (μCT) and mechanical (4-pt bending) analyses of the femur and tibia. Body mass was similar between groups, although exercised mice were leaner (-35% fat mass). Bone mineral density was also similar, while bone mineral content was increased (+7%) in the exercised mice. Femoral midshaft polar moment of inertia was similar between groups, but exercised mice had lower BV/TV (-46%) of the distal femur and greater trabecular spacing (+21%). Exercised femora showed more total displacement (+58%) and post yield displacement (+115%) in bending than controls, and increased material toughness (+40%). Patterns were similar for the tibia. Mechanical data are consistent with high-impact exercise studies, but architectural data are not. Together they suggest that our exercise model may improve bone mechanical properties by redistributing mineral within the skeleton, and not by increasing net bone formation

FOUNDRIES OF THE FUTURE:

Since the 1970s, cities world-wide have been witness to radical de-industrialisation. Manufacturing was considered incompatible with urban life and was actively pushed out. As economies have grown, public officials and developers have instinctively shifted their priorities to short-term, high-yielding land uses such as offices, retail space and housing. Inner-city growth from New York to London and even Seoul have generally come at the expense of land uses such as manufacturing or logistics. Despite the odds, manufacturing is not in terminal decay in western cities. On the contrary, it is at the opening of a new chapter. Urban manufacturing can help cities to be more innovative, circular, inclusive and resilient. Recently, with increasing interest in the circular economy, with cleaner and more compact technology, with more progressive building codes for mixed use, with increasing awareness of the impacts of social inequality and with a clearer understanding of the value chains between the trade of material and immaterial goods, cities across the world are realising that manufacturing has an important place in the 21st century urban economy. While both enthusiasm for making is increasing and the value of manufacturing is becoming increasingly evident in cities, the topic remains extremely complex and challenging to manage. This book attempts to shed light on the ways manufacturing can address urban challenges, it exposes constraints for the manufacturing sector and provides fifty patterns for working with urban manufacturing. This book has been written as a manual to help politicians, public authorities, planners, designers and community organisations to be able to plan, discuss and collaborate by developing more productive urban manufacturing. The book is split into two parts.  We first cover an abridged history of the late nineteenth and early twentieth centuries, noting how European cities evolved rapidly by harnessing manufacturing, and then how the late twentieth century led to a radical shift in how cities work and think. We’re now at a crossroads between actors that do not see the need for manufacturing in cities and those that consider it vital for a prosperous urban future. Part of the tension comes from the fact that manufacturing is considered a ‘weak land use’ compared to activities such as real-estate development, which has been considered more financially attractive by many actors in the private and public sector. This real estate-oriented development narrative is increasingly regarded as short-sighted, but will not change without an alternative vision. We have therefore elaborated a narrative on how urban manufacturing responds to four specific challenges facing cities and how in turn manufacturing needs cities. In practice, planning and design for a topic like this is highly challenging. The second part of the book is intended as a handbook. By synthesising our research and fieldwork conducted in a number of cities, we have encountered many similarities in terms of problems, challenges and solutions for urban manufacturing. Inspired by the seminal 1977 book, ‘A Pattern Language’ we have translated our findings into fifty patterns which help render the diversity of issues concerning manufacturing more tangible. As both teamwork and negotiation are necessary, exercises and methods are provided to use the patterns. Finally, we have set out twelve key action areas as possible starting points for supporting urban manufacturing

The effect of external loads and biological sex on coupling variability during load carriage.

BackgroundLoad carriage is a fundamental requirement for military personnel that commonly results in lower-limb injuries. Coupling variability represents a potential injury mechanism for such repetitive tasks and its unknown whether external loads and biological sex affect coupling variability during load carriage.Research questionIs there a sex-by-load interaction during load carriage at self-selected walking speeds?MethodsTwenty-six participants (13 males, 13 females) completed three 10-minute treadmill-based trials wearing body-borne external load (0 %BM, 20 %BM, and 40 %BM) at load-specific self-selected walking speeds. A Vicon motion capture system tracked markers with a lower-body direct-kinematic model calculating sagittal-plane segment kinematics of the thigh, shank, and foot across 19 strides. Continuous relative phase standard deviation (CRPv) provided a measure of coupling variability for each coupling angle (Thigh-Shank and Shank-Foot). The CRPv for each load and sex was compared using statistical parametric mapping repeated measures ANOVA and paired t tests.ResultsSignificant sex-by-load interactions were reported for the Thigh-Shank coupling. Males demonstrated no significant load differences in CRPv, however, females displayed significantly higher CRPv in the 40 %BM than the 0 %BM condition. A significant main effect of load was observed in the Shank-Foot coupling, with the 40 %BM having significantly greater CRPv than the other load conditions.SignificanceBoth biological sex and external loads significantly affected CRPv during load carriage at self-selected walking speeds. Females demonstrated greater CRPv at the heavier loads, suggesting that the perturbation from the heavier mass increases coupling variability, which may also be amplified by a greater total passive load due to their relatively higher adipose tissue compared to males. The consistent CRPv in males suggests that higher relative loads may be required to change coupling variability. Collectively, these results suggest that external load affects the coupling variability of males and females differently, providing potential for injury screening and monitoring programs

Foreign Capital Inflow, Skilled-Unskilled Wage Inequality and Unemployment of Unskilled Labour in a Fair Wage Model

This paper has developed a three-sector general equilibrium framework that explains unemployment of both skilled and unskilled labour. Unemployment of unskilled labour is of the Harris-Todaro (1970) type while unemployment of skilled labour is caused due to the validity of the FWH in the high-skill sector. There are two types of capital one of which is specific to the primary export sector while the other moves freely among the different sectors. Inflows of foreign capital of either type unambiguously improve the economic conditions of the unskilled working class. However, the effects on the skilled-unskilled wage inequality and the extent of unemployment of both types of labour crucially hinge on the properties implied by the efficiency function of the skilled workers

Membrane Potentials Regulating GPCRs:Insights From Experiments and Molecular Dynamics Simulation

G-protein coupled receptors (GPCRs) form the largest class of membrane proteins in humans and the targets of most present drugs. Membrane potential is one of the defining characteristics of living cells. Recent work has shown that the membrane voltage, and changes thereof, modulates signal transduction and ligand binding in GPCRs. As it may allow differential signalling patterns depending on tissue, cell type, and the excitation status of excitable cells, GPCR voltage sensitivity could have important implications for their pharmacology. This review summarises recent experimental insights on GPCR voltage regulation and the role of molecular dynamics simulations in identifying the structural basis of GPCR voltage-sensing. We discuss the potential significance for drug design on GPCR targets from excitable and non-excitable cells

Conserving the birds of Uganda's Banana-Coffee Arc: Land Sparing and Land Sharing Compared

Reconciling the aims of feeding an ever more demanding human population and conserving biodiversity is a difficult challenge. Here, we explore potential solutions by assessing whether land sparing (farming for high yield, potentially enabling the protection of non-farmland habitat), land sharing (lower yielding farming with more biodiversity within farmland) or a mixed strategy would result in better bird conservation outcomes for a specified level of agricultural production. We surveyed forest and farmland study areas in southern Uganda, measuring the population density of 256 bird species and agricultural yield: food energy and gross income. Parametric non-linear functions relating density to yield were fitted. Species were identified as "winners" (total population size always at least as great with agriculture present as without it) or "losers" (total population sometimes or always reduced with agriculture present) for a range of targets for total agricultural production. For each target we determined whether each species would be predicted to have a higher total population with land sparing, land sharing or with any intermediate level of sparing at an intermediate yield. We found that most species were expected to have their highest total populations with land sparing, particularly loser species and species with small global range sizes. Hence, more species would benefit from high-yield farming if used as part of a strategy to reduce forest loss than from low-yield farming and land sharing, as has been found in Ghana and India in a previous study. We caution against advocacy for high-yield farming alone as a means to deliver land sparing if it is done without strong protection for natural habitats, other ecosystem services and social welfare. Instead, we suggest that conservationists explore how conservation and agricultural policies can be better integrated to deliver land sparing by, for example, combining land-use planning and agronomic support for small farmers

Mechanical differences between men and women during overground load carriage at self-selected walking speeds

Few studies have directly compared physical responses to relative loading strategies between men and women during overground walking. This study aimed to compare gait mechanics of men and women during overground load carriage. A total of 30 participants (15 male, 15 female) completed three 10-min walking trials while carrying external loads of 0%, 20% and 40% of body mass at a self-selected walking speed. Lower-body motion and ground reaction forces were collected using a three-dimensional motion capture system and force plates, respectively. Female participants walked with a higher cadence (p = 0.002) and spent less absolute time in stance (p = 0.010) but had similar self-selected walking speed (p = 0.750), which was likely due to the female participants being shorter than the male participants. Except for ankle plantarflexion moments, there were no sex differences in spatiotemporal, kinematic, or kinetic variables (p > 0.05). Increasing loads resulted in significantly lower self-selected walking speed, greater stance time, and changes in all joint kinematics and kinetics across the gait cycle (p 0.05). In conclusion, there were few differences between sexes in walking mechanics during overground load carriage. The changes identified in this study may inform training programs to increase load carriage performance