Development of a Novel Biological Intervertebral Disc Scaffold

Back pain is a major public health issue in our society, and is strongly correlated with the degeneration of intervertebral discs (IVDs). Current therapies are conservative or surgical, and no attempt to regenerate the IVD. The first goal of our project is to create a fully decellularized bovine caudal IVD to be used as a scaffold on which to seed adult human stem cells in an attempt to engineer a healthy, replacement IVD for patients suffering from IVD degeneration and lower back pain. The goal of decellularization is to eliminate DNA content while retaining glycosaminoglycan (GAG) content. Eliminating DNA content will prevent a foreign body response by the host\u27s immune system once the IVD is implanted. GAG is responsible for forming interfibrillar bridges with collagen fibrils and thus assisting in resisting compressive and tensile forces. By retaining GAG content in our decellularized IVDs we will maintain structural integrity of the extracellular matrix. The IVDs closest to the base of the bovine tail were targeted, because they are similar in size and biochemistry to the human IVD. We use a mix of conventional methods including freeze thaw, sonication and agitation in a solution of sodium dodecyl sulfate (SDS) and ethylene diamine tetraacetic acid (EDTA). After decellularization, half of each IVD was placed in a tissue cassette and put formalin in preparation for histological analysis, and the other half was frozen prior to biochemical analysis (DMMB and PicoGreen assay). Our results thus far are promising in eliminating DNA content but show we have a large room for improvement in retaining GAG content

Chirality of tensor perturbations for complex values of the Immirzi parameter

In this paper we generalise previous work on tensor perturbations in a de Sitter background in terms of Ashtekar variables to cover all complex values of the Immirzi parameter gamma (previous work was restricted to imaginary gamma). Particular attention is paid to the case of real gamma. Following the same approach as in the imaginary case, we can obtain physical graviton states by invoking reality and torsion free conditions. The Hamiltonian in terms of graviton states has the same form whether gamma has a real part or not; however changes occur for the vacuum energy and fluctuations. Specifically, we observe a gamma dependent chiral asymmetry in the vacuum fluctuations only if gamma has an imaginary part. Ordering prescriptions also change this asymmetry. We thus present a measurable result for CMB polarisation experiments that could shed light on the workings of quantum gravity.Comment: 6 pages, 1 figur

E-Voting in an ubicomp world: trust, privacy, and social implications

The advances made in technology have unchained the user from the desktop into interactions where access is anywhere, anytime. In addition, the introduction of ubiquitous computing (ubicomp) will see further changes in how we interact with technology and also socially. Ubicomp evokes a near future in which humans will be surrounded by “always-on,” unobtrusive, interconnected intelligent objects where information is exchanged seamlessly. This seamless exchange of information has vast social implications, in particular the protection and management of personal information. This research project investigates the concepts of trust and privacy issues specifically related to the exchange of e-voting information when using a ubicomp type system

Surface terms, Asymptotics and Thermodynamics of the Holst Action

We consider a first order formalism for general relativity derived from the Holst action. This action is obtained from the standard Palatini-Hilbert form by adding a topological-like term and can be taken as the starting point for loop quantum gravity and spin foam models. The equations of motion derived from the Holst action are, nevertheless, the same as in the Palatini formulation. Here we study the form of the surface terms of the action for general boundaries as well as the symplectic current in the covariant formulation of the theory. Furthermore, we analyze the behavior of the surface terms in asymptotically flat space-times. We show that the contribution to the symplectic structure from the Holst term vanishes and one obtains the same asymptotic expressions as in the Palatini action. It then follows that the asymptotic Poincare symmetries and conserved quantities such as energy, linear momentum and relativistic angular momentum found here are equivalent to those obtained from the standard Arnowitt, Deser and Misner formalism. Finally, we consider the Euclidean approach to black hole thermodynamics and show that the on-shell Holst action, when evaluated on some static solutions containing horizons, yields the standard thermodynamical relations.Comment: 16 page

Selective laser sintering of hydroxyapatite reinforced polyethylene composites for bioactive implants and tissue scaffold development

Selective laser sintering (SLS) has been investigated for the production of bioactive implants and tissue scaffolds using composites of high-density polyethylene (HDPE) reinforced with hydroxyapatite (HA) with the aim of achieving the rapid manufacturing of customized implants. Single-layer and multilayer block specimens made of HA-HDPE composites with 30 and 40 vol % HA were sintered successfully using a CO2 laser sintering system. Laser power and scanning speed had a significant effect on the sintering behaviour. The degree of particle fusion and porosity were influenced by the laser processing parameters, hence control can be attained by varying these parameters. Moreover, the SLS processing allowed exposure of HA particles on the surface of the composites and thereby should provide bioactive products. Pores existed in the SLS-fabricated composite parts and at certain processing parameters a significant fraction of the pores were within the optimal sizes for tissue regeneration. The results indicate that the SLS technique has the potential not only to fabricate HA-HDPE composite products but also to produce appropriate features for their application as bioactive implants and tissue scaffolds

Dopamine D_2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive 4 nicotinic receptors via a cholinergic-dependent mechanism

Recent studies suggest that high-affinity neuronal nicotinic acetylcholine receptors (nAChRs) containing α4 and β2 subunits (α4β2*) functionally interact with G-protein-coupled dopamine (DA) D_2 receptors in basal ganglia. We hypothesized that if a functional interaction between these receptors exists, then mice expressing an M2 point mutation (Leu9'Ala) rendering 4 nAChRs hypersensitive to ACh may exhibit altered sensitivity to a D_2-receptor agonist. When challenged with the D_(2)R agonist, quinpirole (0.5–10 mg/kg), Leu9'Ala mice, but not wild-type (WT) littermates, developed severe, reversible motor impairment characterized by rigidity, catalepsy, akinesia, and tremor. While striatal DA tissue content, baseline release, and quinpirole-induced DA depletion did not differ between Leu9'Ala and WT mice, quinpirole dramatically increased activity of cholinergic striatal interneurons only in mutant animals, as measured by increased c-Fos expression in choline acetyltransferase (ChAT)-positive interneurons. Highlighting the importance of the cholinergic system in this mouse model, inhibiting the effects of ACh by blocking muscarinic receptors, or by selectively activating hypersensitive nAChRs with nicotine, rescued motor symptoms. This novel mouse model mimics the imbalance between striatal DA/ACh function associated with severe motor impairment in disorders such as Parkinson’s disease, and the data suggest that a D_(2)R–α4*-nAChR functional interaction regulates cholinergic interneuron activity.—Zhao-Shea, R., Cohen, B. N., Just, H., McClure-Begley, T., Whiteaker, P., Grady, S. R., Salminen, O., Gardner, P. D., Lester, H. A., Tapper, A. R. Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive α4 nicotinic receptors via a cholinergic-dependent mechanism

Automatic Segmentation of Muscle Tissue and Inter-muscular Fat in Thigh and Calf MRI Images

Magnetic resonance imaging (MRI) of thigh and calf muscles is one of the most effective techniques for estimating fat infiltration into muscular dystrophies. The infiltration of adipose tissue into the diseased muscle region varies in its severity across, and within, patients. In order to efficiently quantify the infiltration of fat, accurate segmentation of muscle and fat is needed. An estimation of the amount of infiltrated fat is typically done visually by experts. Several algorithmic solutions have been proposed for automatic segmentation. While these methods may work well in mild cases, they struggle in moderate and severe cases due to the high variability in the intensity of infiltration, and the tissue's heterogeneous nature. To address these challenges, we propose a deep-learning approach, producing robust results with high Dice Similarity Coefficient (DSC) of 0.964, 0.917 and 0.933 for muscle-region, healthy muscle and inter-muscular adipose tissue (IMAT) segmentation, respectively.Comment: 9 pages, 4 figures, 2 tables, MICCAI 2019, the 22nd International Conference on Medical Image Computing and Computer Assisted Interventio

Quantum geometrodynamics creates new problems

The development of last years in quantum geometrodynamics highlights new problems which were not obvious in its first formulation proposed by Wheeler and DeWitt. At the first stage the main task was to apply known quantization schemes to gravitational field or a certain cosmological model. This way has led to the realization of the fact that a quantum description of the Universe is impossible without implicit or explicit indication to a reference frame presented by some medium, filling the whole Universe, with its own equation of state and thermodynamical properties. Thus the questions arise, should one seek for a "privileged" reference frame or consider all the variety of gauge conditions and appropriate solutions for the wave function? It is worth noting that thermodynamical properties of such a quantum Universe would also depend on a chosen reference frame to some extent. So, we need a self-consistent quantum theoretical and thermodynamical description of the Universe.Comment: 5 pages, talk presented at the XIII Russian Gravitational Conference, Moscow, June 2008, a reference correcte

Increase in hypoglycaemia and hyperglycaemia in people with diabetes admitted to hospital during COVID-19 pandemic

BACKGROUND: We used detailed information on patients with diabetes admitted to hospital to determine differences in clinical outcomes before and during the COVID-19 pandemic in the UK. METHODS: The study used electronic patient record data from Imperial College Healthcare NHS Trust. Hospital admission data for patients coded for diabetes was analysed over three time periods: pre-pandemic (31st January 2019-31st January 2020), Wave 1 (1st February 2020-30th June 2020), and Wave 2 (1st September 2020-30th April 2021). We compared clinical outcomes including glycaemia and length of stay. RESULTS: We analysed data obtained from 12,878, 4008 and 7189 hospital admissions during the three pre-specified time periods. The incidence of Level 1 and Level 2 hypoglycaemia was significantly higher during Waves 1 and 2 compared to the pre-pandemic period (25 % and 25.1 % vs. 22.9 % for Level 1 and 11.7 % and 11.5 % vs. 10.3 % for Level 2). The incidence of hyperglycaemia was also significantly higher during the two waves. The median hospital length of stay increased significantly (4.1[1.6, 9.8] and 4.0[1.4, 9.4] vs. 3.5[1.2, 9.2] days). CONCLUSIONS: During the COVID-19 pandemic in the UK, hospital in-patients with diabetes had a greater number of hypoglycaemic/hyperglycaemic episodes and an increased length of stay when compared to the pre-pandemic period. This highlights the necessity for a focus on improved diabetes care during further significant disruptions to healthcare systems and ensuring minimisation of the impact on in-patient diabetes services. SUMMARY: Diabetes is associated with poorer outcomes from COVID-19. However the glycaemic control of inpatients before and during the COVID-19 pandemic is unknown. We found the incidence of hypoglycaemia and hyperglycaemia was significantly higher during the pandemic highlighting the necessity for a focus on improved diabetes care during further pandemics