Quantitative Imaging Biomarkers of Knee Cartilage Composition

For a long time, radiography and subsequently conventional magnetic resonance imaging (MRI) were used as imaging biomarkers for evaluating cartilage morphological disease state in osteoarthritis (OA). Because research is switching its focus towards disease modification or even prevention to target OA at an early stage, imaging techniques that measure cartilage composition rather than its morphology became of interest. Several MRI and computed tomography (CT) based quantitative imaging biomarkers for cartilage composition were developed. These techniques were advocated to allow a quantitative measure of the sulphated glycosaminoglycan (sGAG) content, an important composite of the cartilage extracellular matrix. The main aims of this thesis is based have been divided between MRI and CT based quantitative imaging biomarkers since their different stage of application in research. MRI has already been applied in human OA research, whereas CT was still to be translated and implemented in clinical research. The first part of this thesis focused on MRI based techniques and aimed at optimization of image post processing, assessing reproducibility, comparison of different MRI sequences and application in clinical OA research. Since accurate image post processing is of utmost importance to generate reliable and robust quantitative MRI outcomes, an imaging post processing tool was developed and described in chapter 2. This tool corrects for intra-sequence patient motion during acquisition of quantitative MR images, by applying image registration reducing errors and incorrect outcomes. This resulted in 6-14% improvement in accuracy of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) T1 relaxation time. Using image registration, the tool also allows assessment of the same cartilage region throughout multiple MRI acquisitions, which makes analyses less time consuming. Finally, the algorithm also involves a fitting technique which corrects for unreliable quantitative MRI biomarker data by calculating a weighted mean outcome for all voxels in a specific cartilage region based on the inaccuracy of each voxel. Because of these abilities and the fact that this tool could be used in any quantitative MRI biomarker, e.g. T1rho-mapping or T2-mapping, the image post processing tool was used in all chapters in this thesis where MRI based measures were used for cartilage sGAG content. Along with robust image processing tools, the outcomes of the MRI exam itself should also be reproducible in order to be able to apply the particular technique in cross-sectional or longitudinal study designs. Therefore, chapter 3 described a reproducibility study of dGEMRIC acquired at 3 Tesla in early stage knee OA patient. It was shown that dGEMRIC is highly reproducible in terms of results in large cartilage regions, as well as for differentiating between spatial distributions of diverse cartilage quality within a single slice. dGEMRIC can therefore be used as an imaging biomarker in cross-sectional and longitudinal study designs. In addition, a threshold for defining significant changes in dGEMRIC results for longitudinal follow-up was determined. T1rho-mapping has been proposed as a non-contrast-enhanced alternative to dGEMRIC for sGAG quantification in clinical studies. However, no thorough validation has been performed comparing both techniques within the same OA patients using a reference standard for cartilage sGAG. Therefore, in chapter 4 an in vivo comparison and validation study assessing the capability of dGEMRIC and T1rho-mapping was performed. In knee OA patients, dGEMRIC results strongly correlate with cartilage sGAG content, whereas T1rho-mapping did not. Therefore, it appears that T1rho-mapping cannot be regarded as an alternative for dGEMRIC to measure cartilage sGAG content in clinical OA research. It was also shown that resu

A comparative study of Norse palaeodemography in the North Atlantic

Acknowledgements British Academy Global Professorship GP2\190224. The authors would like to thank Ricky Craig, Independent GIS Specialist and Cartographer, Scotland, for preparing Figure 1, the map.Peer reviewe

The preparation and characterisation of monomeric and linked metal carbonyl clusters containing the closo-Si2Co4 pseudo-octahedral core

PhSiH3 reacts with [Co₄(CO)₁₂] at 50 °C in hydrocarbon solvents to give [(µ₄-SiPh)₂Co₄(CO)₁₁], 2c, shown by an X-ray crystal structure determination to have a pseudo-octahedral Si₂Co₄ core. Substituted aryl-silanes behaved similarly. Mixtures of PhSiH₃, H₃SiC₆H₄SiH₃ and [Co₄(CO)₁₂] in a ca. 2 1 2 ratio gave the dimeric cluster [{Co₄(µ₄-SiPh)(CO)₁₁Si}₂C₆H₄], 3a, which has the two Si₂Co₄ cores linked by a C₆H₄ group to give a rigid molecule which an X-ray structure analysis shows to be over 23 Å long. Related dimers linked by –(CH₂)₈– groups were isolated from mixtures of PhSiH₃, α ,ω-(H₃Si)₂(CH₂)₈ and [Co₄(CO)₁₂]. Electrochemical studies show the two cluster units in 3a do not interact electronically

Outcome of traumatic thoracolumbar spine fractures in elderly:A systematic review

Introduction: Adequate guidelines for treatment of people over 65 years, suffering traumatic thoracolumbar spine fractures without neurologic deficit, are currently lacking. Research question: The aim of this study was to systematically review the available literature regarding the outcome of conservative and surgical treatment of thoracolumbar spinal trauma in elderly patients. Material and methods: A systematic review according the PRISMA guidelines was performed. Pubmed, Web of Science, EMBASE and the Cochrane Central register were searched until June 2021. Risk of bias of the included studies was evaluated. Clinical and radiological results, as well as complications of conservative or surgical treatment were reviewed. Results: Six articles were included (one prospective randomized trial, two prospective and three retrospective cohort studies). In these studies conflicting results were observed with regard to pain, radiological results and complications following both conservative and surgical treatment strategies for thoracolumbar spine fractures in elderly. Discussion and conclusion: Treatment of thoracolumbar fractures in elderly should focus on early mobilization to reduce complications and hospital stay. This may improve functional outcome and prevent worsening of frailty in this vulnerable group of patients. To elucidate the optimal treatment for elderly patient with thoracolumbar fractures, future research should focus on patient specific treatment rather than the mere difference between outcome of surgical and conservative treatment.</p

Outcome of traumatic thoracolumbar spine fractures in elderly:A systematic review

Introduction: Adequate guidelines for treatment of people over 65 years, suffering traumatic thoracolumbar spine fractures without neurologic deficit, are currently lacking. Research question: The aim of this study was to systematically review the available literature regarding the outcome of conservative and surgical treatment of thoracolumbar spinal trauma in elderly patients. Material and methods: A systematic review according the PRISMA guidelines was performed. Pubmed, Web of Science, EMBASE and the Cochrane Central register were searched until June 2021. Risk of bias of the included studies was evaluated. Clinical and radiological results, as well as complications of conservative or surgical treatment were reviewed. Results: Six articles were included (one prospective randomized trial, two prospective and three retrospective cohort studies). In these studies conflicting results were observed with regard to pain, radiological results and complications following both conservative and surgical treatment strategies for thoracolumbar spine fractures in elderly. Discussion and conclusion: Treatment of thoracolumbar fractures in elderly should focus on early mobilization to reduce complications and hospital stay. This may improve functional outcome and prevent worsening of frailty in this vulnerable group of patients. To elucidate the optimal treatment for elderly patient with thoracolumbar fractures, future research should focus on patient specific treatment rather than the mere difference between outcome of surgical and conservative treatment.</p

Examining Museum Visits as Literacy Events: the role of mediators

Museum exhibitions are literacy rich environments. Visitors may engage with a range of texts including texts that constitute the exhibition objects themselves, those that convey information about the objects and those that instruct visitors about how the visitors are expected by the museum to navigate through the exhibition. The ways in which visitors engage with these diverse texts are important defining factors of the visitors museum experience. For museums, understanding how texts in their exhibitions are influencing the museum experience, and the possibility of a museum experience for the broad public community is important in the fulfilment of their public mission as cultural and education institutions. In this paper, we adopt a view of literacy as a social practice, the perspective of New Literacy Studies (NLS), that offers a fruitful way for museums to consider the interactions between exhibition texts and their audiences. Such considerations, we argue, can inform museums approaches to broadening their visitor demographics to more strongly fulfill their public mission. We show that the goals of NLS resonate with some of the goals of the New Museology movement in museum studies, a movement that aims to democratize what museums represent and how

Lifting the Shroud: Government, Investment Banks and Power in Post Financial Crisis United Kingdom - A critical deconstruction of the relationship between government and investment banks in the United Kingdom post global financial crisis (2007 – 2011)

The late 2000s Global Financial Crisis swept the advanced world and spilled into the developing, creating chaos in its wake. At the crux of the crisis were the high-risk activities of investment banks in the developed world – and especially United Kingdom. Since then, academic and public discussion has revolved around the questionable relationship between investment banks and government that resulted in subpar regulation and the costly bank ‘bailouts’ of 2008 and 2009. What this thesis will to do is holistically assess how the power relationship between British investment banks and the United Kingdom government has evolved since the crisis, utilising Doris Fuchs’ Three Dimensional Approach to Business Power and Governance and a wide array of research to address those structural, instrumental and discursive elements of business power

Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans

In this double-blind, cross-over, placebo-controlled, randomized study, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in conjunction with placebo and once with granulocyte colony-stimulating factor (G-CSF; 5 microg/kg). In group 1, G-CSF was administered intravenously 2 hours before endotoxin challenge; in group 2, G-CSF was administered subcutaneously 24 hours before endotoxin challenge. In group 1, G-CSF significantly enhanced the release of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors. In group 2, G-CSF significantly reduced IL-8 concentrations and modestly attenuated TNF and IL-6 levels. In this group, IL-1ra and soluble TNF receptors were enhanced by G-CSF pretreatment and lipopolysaccharide (LPS)-induced soluble TNF receptor release was further augmented, whereas LPS-induced IL-1ra concentrations remained unaltered. Both pretreatments with G-CSF increased LPS-induced peripheral neutrophilia; the expression of CD11b, CD18, and CD67; and the release of elastase and lactoferrin. Both pretreatments also down-regulated neutrophil L-selectin expression and prevented the endotoxin-induced pulmonary neutrophil accumulation during the first 2 hours after endotoxin challenge. These data indicate that two different pretreatments with G-CSF result in differential effects on LPS-induced cytokine release but similar effects on LPS-induced neutrophil activation and changes in expression of cell surface molecules. Finally, regardless of the effects of G-CSF on LPS-induced cytokine release, G-CSF blocks LPS-induced pulmonary granulocyte accumulatio

Differentiable but exact formulation of density-functional theory

The universal density functional F of density-functional theory is a complicated and ill-behaved function of the density—in particular, F is not differentiable, making many formal manipulations more complicated. While F has been well characterized in terms of convex analysis as forming a conjugate pair (E, F) with the ground-state energy E via the Hohenberg–Kohn and Lieb variation principles, F is nondifferentiable and subdifferentiable only on a small (but dense) subset of its domain. In this article, we apply a tool from convex analysis, Moreau–Yosida regularization, to construct, for any ε > 0, pairs of conjugate functionals (ε E, ε F) that converge to (E, F) pointwise everywhere as ε → 0+, and such that ε F is (Fréchet) differentiable. For technical reasons, we limit our attention to molecular electronic systems in a finite but large box. It is noteworthy that no information is lost in the Moreau–Yosida regularization: the physical ground-state energy E(v) is exactly recoverable from the regularized ground-state energy ε E(v) in a simple way. All concepts and results pertaining to the original (E, F) pair have direct counterparts in results for (ε E, ε F). The Moreau–Yosida regularization therefore allows for an exact, differentiable formulation of density-functional theory. In particular, taking advantage of the differentiability of ε F, a rigorous formulation of Kohn–Sham theory is presented that does not suffer from the noninteracting representability problem in standard Kohn–Sham theory