Interventions to Reduce Spasticity and Improve Function in People With Chronic Incomplete Spinal Cord Injury: Distinctions Revealed by Different Analytical Methods.

Background. Spinal cord injury (SCI) results in impaired function, and ankle joint spasticity is a common secondary complication. Different interventions have been trialed with variable results. Objective. We investigated the effects of pharmacological and physical (locomotor training) interventions on function in people living with incomplete motor function loss caused by SCI and used different analytical techniques to understand whether functional levels affect recovery with different interventions. Methods. Participants with an incomplete SCI were assigned to 3 groups: no intervention, Lokomat, or tizanidine. Outcome measures were the 10-m walk test, 6-minute walk test, and the Timed Up and Go. Participants were classified in 2 ways: (1) based on achieving an improvement above the minimally important difference (MID) and (2) using growth mixture modeling (GMM). Functional levels of participants who achieved the MID were compared and random coefficient regression (RCR) was used to assess recovery in GMM classes. Results. Overall, walking speed and endurance improved, with no difference between interventions. Only a small number of participants achieved the MID. Both MID and GMM-RCR analyses revealed that tizanidine improved endurance in high-functioning participants. GMM-RCR classification also showed that speed and mobility improved after locomotor training. Conclusions. Improvements in function were achieved in a limited number of people with SCI. Using the MID and GMM techniques, differences in responses to interventions between high-and low-functioning participants could be identified. These techniques may, therefore, have potential to be used for characterizing therapeutic effects resulting from different interventions

Murine myoblast migration: influence of replicative ageing and nutrition

Cell migration is central to skeletal muscle repair following damage. Leucine and β-Hydroxy β-methylbutyric acid (HMB) are supplements consumed for recovery from muscle damaging exercise in humans, however, their impact on muscle cell migration with age is not yet understood. We hypothesised that replicatively aged (“aged”; P46–P48) myoblasts would be less efficient at basal and supplemented repair versus parental controls (“control”; P12–P16). Aged and control myoblasts were scratch-damaged and migration velocity, directionality and distance assessed over 48 h in the absence and presence of leucine (10 mM) or HMB (10 mM) ± PI3K/Akt (LY294002 10 μM), ERK (PD98059 5 μM) or mTOR (rapamycin 0.5 μM) inhibition. Opposing our hypothesis, aged cells displayed increased velocities, directionality and distance migrated (P < 0.001) versus control. Leucine and HMB significantly increased (P < 0.001) the same parameters in control cells. The supplements were with smaller, albeit significant impact on aged cell velocity (P < 0.001) and in the presence of HMB only, distance (P = 0.041). Inhibitor studies revealed that, PI3K and ERK activation were essential for velocity, directionality and migration distance of aged cells in basal conditions, whereas mTOR was important for directionality only. While PI3K activation was critical for all parameters in control cells (P < 0.001), inhibition of ERK or mTOR improved, rather than reduced, control cell migration distance. Enhanced basal velocity, directionality and distance in aged cells required ERK and PI3K activation. By contrast, in control cells, basal migration was underpinned by PI3K activation, and facilitated by leucine or HMB supplementation, to migration levels seen in aged cells. These data suggest that replicatively aged myoblasts are not anabolically resistant per se, but are capable of efficient repair, underpinned by altered signaling pathways, compared with unaged control myoblasts

Molecular footprints of the Holocene retreat of dwarf birch in Britain

© 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

YouTube as a source of information for patients considering surgery for ulcerative colitis

© 2017 Elsevier Inc. Background With the range of health information online, assessing the resources that patients access may improve the content of preoperative information. Our aim was to assess the content of the most viewed videos on YouTube related to surgery for ulcerative colitis (UC). Methods YouTube was searched for videos containing information on surgery for UC. The 50 most viewed videos were identified and user interaction analyzed. Upload source was classified as patient, individual health care professional (HCP), or hospital/professional association. Video content was categorized using an inductive thematic analysis on a purposive sample list of videos. The overarching theme of each video was classified once data saturation was achieved. Results Thirty videos were uploaded by patients, 15 by hospitals and 5 by HCPs. Seventeen videos (34%) discussed life after surgery. Sixteen of these were uploaded by patients who had previously undergone surgery for UC. No videos of this theme were uploaded by HCPs. Ten videos (20%) described a number of different operations. Other themes identified were alternative health therapies (12%), colonoscopy (12%), life with UC (8%), miscellaneous (8%), and education for HCPs (6%). Patient uploaded videos had significantly more comments (P = 0.0079), with 28% of comments on patient videos being users requesting further information. Conclusions Understanding the sequelae of surgery is most important to preoperative patients. There are a lack of professional videos addressing this topic on YouTube. HCPs must participate in the production of videos and adapt preoperative consultations to address common preoperative concerns

Scavenger 0.1: A Theorem Prover Based on Conflict Resolution

This paper introduces Scavenger, the first theorem prover for pure first-order logic without equality based on the new conflict resolution calculus. Conflict resolution has a restricted resolution inference rule that resembles (a first-order generalization of) unit propagation as well as a rule for assuming decision literals and a rule for deriving new clauses by (a first-order generalization of) conflict-driven clause learning.Comment: Published at CADE 201

Reflections and Experiences of a Co-Researcher involved in a Renal Research Study

Background Patient and Public Involvement (PPI) is seen as a prerequisite for health research. However, current Patient and public involvement literature has noted a paucity of recording of patient and public involvement within research studies. There have been calls for more recordings and reflections, specifically on impact. Renal medicine has also had similar criticisms and any reflections on patient and public involvement has usually been from the viewpoint of the researcher. Roles of patient and public involvement can vary greatly from sitting on an Advisory Group to analysing data. Different PPI roles have been described within studies; one being a co-researcher. However, the role of the co-researcher is largely undefined and appears to vary from study to study. Methods The aims of this paper are to share one first time co-researcher's reflections on the impact of PPI within a mixed methods (non-clinical trial) renal research study. A retrospective, reflective approach was taken using data available to the co-researcher as part of the day-to-day research activity. Electronic correspondence and documents such as meeting notes, minutes, interview thematic analysis and comments on documents were re-examined. The co-researcher led on writing this paper. Results This paper offers a broad definition of the role of the co-researcher. The co-researcher reflects on undertaking and leading on the thematic analysis of interview transcripts, something she had not previously done before. The co-researcher identified a number of key themes; the differences in time and responsibility between being a coresearcher and an Advisory Group member; how the role evolved and involvement activities could match the co-researchers strengths (and the need for flexibility); the need for training and support and lastly, the time commitment. It was also noted that it is preferable that a co-researcher needs to be involved from the very beginning of the grant application. Conclusions The reflections, voices and views of those undertaking PPI has been largely underrepresented in the literature. The role of co-researcher was seen to be rewarding but demanding, requiring a large time commitment. It is hoped that the learning from sharing this experience will encourage others to undertake this role, and encourage researchers to reflect on the needs of those involved.Peer reviewedFinal Published versio

Gut thinking: the gut microbiome and mental health beyond the head

Background: In recent decades, dominant models of mental illness have become increasingly focused on the head, with mental disorders being figured as brain disorders. However, research into the active role that the microbiome-gut-brain axis plays in affecting mood and behaviour may lead to the conclusion that mental health is more than an internalised problem of individual brains. Objective: This article explores the implications of shifting understandings about mental health that have come about through research into links between the gut microbiome and mental health problems such as depression and anxiety. It aims to analyse the different ways that the lines between mind and body and mental and physical health are re-shaped by this research, which is starting to inform clinical and public understanding. Design: As mental health has become a pressing issue of political and public concern it has become increasingly constructed in socio-cultural and personal terms beyond clinical spaces, requiring a conceptual response that exceeds biomedical inquiry. This article argues that an interdisciplinary critical medical humanities approach is well positioned to analyse the impact of microbiome-gut-brain research on conceptions of mind. Results: The entanglement of mind and matter evinced by microbiome-gut-brain axis research potentially provides a different way to conceptualise the physical and social concomitants of mental distress. Conclusion: Mental health is not narrowly located in the head but is assimilated by the physical body and intermingled with the natural world, requiring different methods of research to unfold the meanings and implications of gut thinking for conceptions of human selfhood

Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases

The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours

Vector boson pair production at the LHC

We present phenomenological results for vector boson pair production at the LHC, obtained using the parton-level next-to-leading order program MCFM. We include the implementation of a new process in the code, pp -> \gamma\gamma, and important updates to existing processes. We incorporate fragmentation contributions in order to allow for the experimental isolation of photons in \gamma\gamma, W\gamma, and Z\gamma production and also account for gluon-gluon initial state contributions for all relevant processes. We present results for a variety of phenomenological scenarios, at the current operating energy of \sqrt{s} = 7 TeV and for the ultimate machine goal, \sqrt{s} = 14 TeV. We investigate the impact of our predictions on several important distributions that enter into searches for new physics at the LHC.Comment: 35 pages, 14 figure

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass