Huntington's disease: An immune perspective

Copyright © 2011 Annapurna Nayaketal. This article has been made available through the Brunel Open Access Publishing Fund.Huntington's disease (HD) is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. The neurodegeneration in HD is also caused by aberrant immune response in the presence of aggregated mutant huntingtin protein. The effects of immune activation in HD nervous system are a relatively unexplored area of research. This paper summarises immunological features associated with development and progression of HD.U. Kishore acknowledges funding via BRIEF and Brunel University’s strategic funding for the Centre of Infection, Immunity and Disease Mechanisms

Decision Tree Analysis as a Supplementary Tool to Enhance Histomorphological Differentiation when Distinguishing Human from Non-human Cranial Bone in both Burnt and Unburnt States: A feasibility study

This feasibility study was undertaken to describe and record the histological characteristics of burnt and unburnt cranial bone fragments from human and non-human bones. Reference series of fully mineralised, transverse sections of cranial bone, from all variables and specimen states were prepared by manual cutting and semi-automated grinding and polishing methods. A photomicrograph catalogue reflecting differences in burnt and unburnt bone from human and non-humans was recorded and qualitative analysis was performed using an established classification system based on primary bone characteristics. The histomorphology associated with human and non-human samples was, for the main part, preserved following burning at high temperature. Clearly, fibro-lamellar complex tissue subtypes, such as plexiform or laminar primary bone, were only present in non-human bones. A decision tree analysis based on histological features provided a definitive identification key for distinguishing human from non-human bone, with an accuracy of 100%. The decision tree for samples where burning was unknown was 96% accurate, and multi-step classification to taxon was possible with 100% accuracy. The results of this feasibility study, strongly suggest that histology remains a viable alternative technique if fragments of cranial bone require forensic examination in both burnt and unburnt states. The decision tree analysis may provide an additional, but vital tool to enhance data interpretation. Further studies are needed to assess variation in histomorphology taking into account other cranial bones, ontogeny, species and burning conditions

Can analyses of electronic patient records be independently and externally validated? The effect of statins on the mortality of patients with ischaemic heart disease: a cohort study with nested case-control analysis

Objective To conduct a fully independent and external validation of a research study based on one electronic health record database, using a different electronic database sampling the same population. Design Using the Clinical Practice Research Datalink (CPRD), we replicated a published investigation into the effects of statins in patients with ischaemic heart disease (IHD) by a different research team using QResearch. We replicated the original methods and analysed all-cause mortality using: (1) a cohort analysis and (2) a case-control analysis nested within the full cohort. Setting Electronic health record databases containing longitudinal patient consultation data from large numbers of general practices distributed throughout the UK. Participants CPRD data for 34 925 patients with IHD from 224 general practices, compared to previously published results from QResearch for 13 029 patients from 89 general practices. The study period was from January 1996 to December 2003. Results We successfully replicated the methods of the original study very closely. In a cohort analysis, risk of death was lower by 55% for patients on statins, compared with 53% for QResearch (adjusted HR 0.45, 95% CI 0.40 to 0.50; vs 0.47, 95% CI 0.41 to 0.53). In case-control analyses, patients on statins had a 31% lower odds of death, compared with 39% for QResearch (adjusted OR 0.69, 95% CI 0.63 to 0.75; vs OR 0.61, 95% CI 0.52 to 0.72). Results were also close for individual statins. Conclusions Database differences in population characteristics and in data definitions, recording, quality and completeness had a minimal impact on key statistical outputs. The results uphold the validity of research using CPRD and QResearch by providing independent evidence that both datasets produce very similar estimates of treatment effect, leading to the same clinical and policy decisions. Together with other non-independent replication studies, there is a nascent body of evidence for wider validity

Metrics with Prescribed Ricci Curvature near the Boundary of a Manifold

Suppose $M$ is a manifold with boundary. Choose a point $o\in\partial M$. We investigate the prescribed Ricci curvature equation \Ric(G)=T in a neighborhood of $o$ under natural boundary conditions. The unknown $G$ here is a Riemannian metric. The letter $T$ in the right-hand side denotes a (0,2)-tensor. Our main theorems address the questions of the existence and the uniqueness of solutions. We explain, among other things, how these theorems may be used to study rotationally symmetric metrics near the boundary of a solid torus $\mathcal T$. The paper concludes with a brief discussion of the Einstein equation on $\mathcal T$.Comment: 13 page

Modelling radiation effects in solids with two-temperature molecular dynamics

The ability to predict the structural modifications of materials resulting from a broad range of irradiation scenarios would have a positive impact on many fields of science and technology. Established techniques for modelling large atomic systems, such as classical molecular dynamics, are limited by the neglect of the electronic degrees of freedom which restricts their application to irradiation events that primarily interact with atomic nuclei. Ab initio methods, on the other hand, include electronic degrees of freedom, but the requisite computational costs restrict their application to relatively small systems. Recent methodological developments aimed at overcoming some of these limitations are based on methods that couple atomistic models to a continuum model for the electronic energy, where energy is exchanged between the nuclei and electrons via electronic stopping and electron-phonon coupling mechanisms. Such two-temperature molecular dynamics models, as they are known, make it practicable to simulate the effects of electronic excitations on systems with millions, or even hundreds of millions, of atoms. They have been used to study laser irradiation of metallic films, swift heavy ion irradiation of metals and semiconductors, and moderately high ion irradiation of metals. In this review we describe the two-temperature molecular dynamics methodology and the various practical considerations required for its implementation. We provide example applications of the model to multiple irradiation scenarios that accommodate electronic excitations. We also describe the challenges of including the effects of the modification of the interatomic interactions, due to the excitation of electrons, in the simulations and how these challenges can be overcome