Modelling the injured spinal cord using 3-dimensional cell cultures; strategies for improving tissue engineered repair

Abstract not available

A 3D <i>in vitro</i> model reveals differences in the astrocyte response elicited by potential stem cell therapies for CNS injury.

Aim: This study aimed to develop a 3D culture model to test the extent to which transplanted stem cells modulate astrocyte reactivity, where exacerbated glial cell activation could be detrimental to CNS repair success. Materials & methods: The reactivity of rat astrocytes to bone marrow mesenchymal stem cells, neural crest stem cells (NCSCs) and differentiated adipose-derived stem cells was assessed after 5 days. Schwann cells were used as a positive control. Results: NCSCs and differentiated Schwann cell-like adipose-derived stem cells did not increase astrocyte reactivity. Highly reactive responses to bone marrow mesenchymal stem cells and Schwann cells were equivalent. Conclusion: This approach can screen therapeutic cells prior to in vivo testing, allowing cells likely to trigger a substantial astrocyte response to be identified at an early stage. NCSCs and differentiated Schwann cell-like adipose-derived stem cells may be useful in treating CNS damage without increasing astrogliosis

Astrocyte alignment in 3D collagen gels increases neurite outgrowth; implications for improving spinal cord repair

A major impediment to tissue engineered repair of CNS damage is the glial scar that forms around implanted graft devices and creates an inhibitory environment for axon growth out of the repair site 1. The glial scar is composed of a 3-dimensional (3D) meshwork of astrocytes which become reactive in response to damage stimuli. Previous studies have shown that longitudinal alignment of astrocytes growing in monolayer is sufficient to direct and enhance the growth of neurites over their surface 2,3. The aim of this work therefore was to develop a 3D culture system in which the effect of astrocyte alignment on neurite growth could be modelled in a spatially relevant environment

The Investigation of Space Charge Dominated Beams in a Synchrotron

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

The DLV System for Knowledge Representation and Reasoning

This paper presents the DLV system, which is widely considered the state-of-the-art implementation of disjunctive logic programming, and addresses several aspects. As for problem solving, we provide a formal definition of its kernel language, function-free disjunctive logic programs (also known as disjunctive datalog), extended by weak constraints, which are a powerful tool to express optimization problems. We then illustrate the usage of DLV as a tool for knowledge representation and reasoning, describing a new declarative programming methodology which allows one to encode complex problems (up to $\Delta^P_3$-complete problems) in a declarative fashion. On the foundational side, we provide a detailed analysis of the computational complexity of the language of DLV, and by deriving new complexity results we chart a complete picture of the complexity of this language and important fragments thereof. Furthermore, we illustrate the general architecture of the DLV system which has been influenced by these results. As for applications, we overview application front-ends which have been developed on top of DLV to solve specific knowledge representation tasks, and we briefly describe the main international projects investigating the potential of the system for industrial exploitation. Finally, we report about thorough experimentation and benchmarking, which has been carried out to assess the efficiency of the system. The experimental results confirm the solidity of DLV and highlight its potential for emerging application areas like knowledge management and information integration.Comment: 56 pages, 9 figures, 6 table

Troubling the exclusive privileges of citizenship: mobile solidarities, asylum seekers, and the right to work

This article discusses asylum seekers and the right to work in the UK. Differential access to the labour market is one of the ways in which the state maintains a distinction between British citizens, who ‘belong’, and non-citizens who do not. While such a policy approach garners widespread support amongst the general public of citizens, it does not go uncontested. This article discusses a UK-based campaign, ‘Let Them Work’, which has sought to influence the government in extending the right to work to asylum seekers. In doing so, it demonstrates the ways in which the stratified regime of citizenship rights is contested politically, and explores how such contestation troubles the exclusive privileges of citizenship by enacting mobile solidarities from marginalised spaces

Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia.

The evolution of established cancers is driven by selection of cells with enhanced fitness. Subclonal mutations in numerous epigenetic regulator genes are common across cancer types, yet their functional impact has been unclear. Here, we show that disruption of the epigenetic regulatory network increases the tolerance of cancer cells to unfavorable environments experienced within growing tumors by promoting the emergence of stress-resistant subpopulations. Disruption of epigenetic control does not promote selection of genetically defined subclones or favor a phenotypic switch in response to environmental changes. Instead, it prevents cells from mounting an efficient stress response via modulation of global transcriptional activity. This "transcriptional numbness" lowers the probability of cell death at early stages, increasing the chance of long-term adaptation at the population level. Our findings provide a mechanistic explanation for the widespread selection of subclonal epigenetic-related mutations in cancer and uncover phenotypic inertia as a cellular trait that drives subclone expansion

A review of the surgical conversion rate and independent management of spinal extended scope practitioners in a secondary care setting

INTRODUCTION Spinal orthopaedic triage aims to reduce unnecessary referrals to surgical consultants, thereby reducing waiting times to be seen by a surgeon and to surgical intervention. This paper presents an evaluation of a spinal orthopaedic triage service in the third largest spinal unit in the UK. METHODS A retrospective service evaluation spanning 2012 to 2014 was undertaken by members of the extended scope practitioner (ESP) team to evaluate the ESPs’ ability to manage patient care independently and triage surgical referrals appropriately. Data collected included rates of independent management, referral rates for surgical consideration and conversion to surgery. Patient satisfaction rates were evaluated retrospectively from questionnaires given to 5% of discharged patients. RESULTS A total of 2,651 patients were seen. The vast majority (92%) of all referrals seen by ESPs were managed independently. Only 8% required either a discussion with a surgeon to confirm management or for surgical review. Of the latter, 81% were considered to be suitable surgical referrals. A 99% satisfaction rate was reported by discharged patients. CONCLUSIONS ESP services in a specialist spinal service are effective in managing spinal conditions conservatively and identifying surgical candidates appropriately. Further research is needed to confirm ESPs’ diagnostic accuracy, patient outcomes and cost effectiveness