273 research outputs found
The effects of B cell depletion on bone turnover in rheumatoid arthritis
PhD ThesisRheumatoid arthritis (RA) is the most prevalent inflammatory joint disease. B cells have a role in both the pathogenesis of RA and the regulation of bone cell activity. Depletion of B cells by the anti-CD20 antibody rituximab (RTX) is a highly effective treatment of RA, which is now well established. However, the role of B-cells in bone turnover is controversial. The aim of this thesis was to investigate the effects of B cell depletion on bone turnover in RA. It is postulated that prolonged B cell depletion in patients with RA may have a beneficial effect on the bone loss that would otherwise be expected in active disease. Furthermore, this affect may be direct through modulation of osteoclastogenesis or indirect through attenuation of systemic inflammation and increased physical activity. Preliminary results in forty-six RA patients six months after RTX indicated that there was a significant suppression in bone resorption accompanied to a lesser degree by an increase in bone formation. However, in a second prospective cohort of forty-five RA patients treated with RTX over twelve months, bone mineral density (BMD) fell at the femur sites, but was maintained at the lumbar spine and forearm. There was a significant increase in bone formation, but no significant change in bone resorption or osteocyte markers. Additionally, the effects of RTX on bone turnover were influenced by vitamin D status, gender and menopausal state. Results of in vitro osteoclastogenesis with peripheral blood mononuclear cells (PBMCs) isolated from the blood of twelve self-reported healthy volunteers; indicated that in vitro B cell depletion via magnetic-activated cell sorting (MACS), significantly increased osteoclast formation. In contrast, PBMCs isolated from the blood of five RA patients, up to twelve months post B cell depletion with RTX, resulted in decreased osteoclast formation using the same standardised culture system. In summary, the results of the pilot study showed that B cell depletion significantly decreased bone resorption and increased bone formation in RA, possibly via a direct effect on osteoclasts and osteoblasts, respectively, or at least partially explained by the decreased inflammation and disease activity. However, this was not confirmed in the prospective study as the results were confounded by a high prevalence of vitamin D deficiency and these patients had significant falls in femur BMD and evidence of higher bone turnover. Furthermore, as there were no control groups it was difficult to establish whether depletion of B cells had in fact slowed down the expected bone loss in these patients. The results of the in vitro experiments indicated that under basal conditions i.e. in healthy subjects, the production of osteoprotegerin by B cells outweighed the production of receptor activator of nuclear factor - κb ligand (RANKL). However, in pro-inflammatory states, where B cells are activated e.g. RA, B cells produce cytokines like RANKL that stimulate osteoclastogenesis resulting in an increased production of osteoclasts. Hence B cell depletion
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in this latter situation caused a reduction in osteoclast generation. Further work is now required to investigate if subsets of pathogenic B cells i.e. not found in healthy individuals are specific to inflammatory bone erosion.South Tees R&D and Roche Products Limited (Welwyn Garden City, UK) providing funding for the prospective trial
Quasi-Topological Field Theories in Two Dimensions as Soluble Models
We study a class of lattice field theories in two dimensions that includes
gauge theories. Given a two dimensional orientable surface of genus , the
partition function is defined for a triangulation consisting of
triangles of area . The reason these models are called
quasi-topological is that depends on , and but not on the
details of the triangulation. They are also soluble in the sense that the
computation of their partition functions can be reduced to a soluble one
dimensional problem. We show that the continuum limit is well defined if the
model approaches a topological field theory in the zero area limit, i.e.,
with finite . We also show that the universality classes of
such quasi-topological lattice field theories can be easily classified.
Yang-Mills and generalized Yang-Mills theories appear as particular examples of
such continuum limits.Comment: 23 pages, 16 figures, uses psbox.te
The Hausdorff dimension in polymerized quantum gravity
We calculate the Hausdorff dimension, , and the correlation function
exponent, , for polymerized two dimensional quantum gravity models. If
the non-polymerized model has correlation function exponent then
where is the susceptibility exponent. This suggests
that these models may be in the same universality class as certain non-generic
branched polymer models.Comment: 10 pages, 1 figure. A meaning-free sentence has been rewritte
Surface tension in an intrinsic curvature model with fixed one-dimensional boundaries
A triangulated fixed connectivity surface model is investigated by using the
Monte Carlo simulation technique. In order to have the macroscopic surface
tension \tau, the vertices on the one-dimensional boundaries are fixed as the
edges (=circles) of the tubular surface in the simulations. The size of the
tubular surface is chosen such that the projected area becomes the regular
square of area A. An intrinsic curvature energy with a microscopic bending
rigidity b is included in the Hamiltonian. We found that the model undergoes a
first-order transition of surface fluctuations at finite b, where the surface
tension \tau discontinuously changes. The gap of \tau remains constant at the
transition point in a certain range of values A/N^\prime at sufficiently large
N^\prime, which is the total number of vertices excluding the fixed vertices on
the boundaries. The value of \tau remains almost zero in the wrinkled phase at
the transition point while \tau remains negative finite in the smooth phase in
that range of A/N^\prime.Comment: 12 pages, 8 figure
Disaggregation of spatial rainfall fields for hydrological modelling
International audienceMeteorological models generate fields of precipitation and other climatological variables as spatial averages at the scale of the grid used for numerical solution. The grid-scale can be large, particularly for GCMs, and disaggregation is required, for example to generate appropriate spatial-temporal properties of rainfall for coupling with surface-boundary conditions or more general hydrological applications. A method is presented here which considers the generation of the wet areas and the simulation of rainfall intensities separately. For the first task, a nearest-neighbour Markov scheme, based upon a Bayesian technique used in image processing, is implemented so as to preserve the structural features of the observed rainfall. Essentially, the large-scale field and the previously disaggregated field are used as evidence in an iterative procedure which aims at selecting a realisation according to the joint posterior probability distribution. In the second task the morphological characteristics of the field of rainfall intensities are reproduced through a random sampling of intensities according to a beta distribution and their allocation to pixels chosen so that the higher intensities are more likely to be further from the dry areas. The components of the scheme are assessed for Arkansas-Red River basin radar rainfall (hourly averages) by disaggregating from 40 km x 40 km to 8 km x 8 km. The wet/dry scheme provides a good reproduction both of the number of correctly classified pixels and the coverage, while the intensitiy scheme generates fields with an adequate variance within the grid-squares, so that this scheme provides the hydrologist with a useful tool for the downscaling of meteorological model outputs. Keywords: Rainfall, disaggregation, General Circulation Model, Bayesian analysi
The flat phase of fixed-connectivity membranes
The statistical mechanics of flexible two-dimensional surfaces (membranes)
appears in a wide variety of physical settings. In this talk we discuss the
simplest case of fixed-connectivity surfaces. We first review the current
theoretical understanding of the remarkable flat phase of such membranes. We
then summarize the results of a recent large scale Monte Carlo simulation of
the simplest conceivable discrete realization of this system \cite{BCFTA}. We
verify the existence of long-range order, determine the associated critical
exponents of the flat phase and compare the results to the predictions of
various theoretical models.Comment: 7 pages, 5 figures, 3 tables. LaTeX w/epscrc2.sty, combined
contribution of M. Falcioni and M. Bowick to LATTICE96(gravity), to appear in
Nucl. Phys. B (proc. suppl.
The Phase Diagram of Crystalline Surfaces
We report the status of a high-statistics Monte Carlo simulation of
non-self-avoiding crystalline surfaces with extrinsic curvature on lattices of
size up to nodes. We impose free boundary conditions. The free energy
is a gaussian spring tethering potential together with a normal-normal bending
energy. Particular emphasis is given to the behavior of the model in the cold
phase where we measure the decay of the normal-normal correlation function.Comment: 9 pages latex (epsf), 4 EPS figures, uuencoded and compressed.
Contribution to Lattice '9
Phase transitions of an intrinsic curvature model on dynamically triangulated spherical surfaces with point boundaries
An intrinsic curvature model is investigated using the canonical Monte Carlo
simulations on dynamically triangulated spherical surfaces of size upto N=4842
with two fixed-vertices separated by the distance 2L. We found a first-order
transition at finite curvature coefficient \alpha, and moreover that the order
of the transition remains unchanged even when L is enlarged such that the
surfaces become sufficiently oblong. This is in sharp contrast to the known
results of the same model on tethered surfaces, where the transition weakens to
a second-order one as L is increased. The phase transition of the model in this
paper separates the smooth phase from the crumpled phase. The surfaces become
string-like between two point-boundaries in the crumpled phase. On the
contrary, we can see a spherical lump on the oblong surfaces in the smooth
phase. The string tension was calculated and was found to have a jump at the
transition point. The value of \sigma is independent of L in the smooth phase,
while it increases with increasing L in the crumpled phase. This behavior of
\sigma is consistent with the observed scaling relation \sigma \sim (2L/N)^\nu,
where \nu\simeq 0 in the smooth phase, and \nu=0.93\pm 0.14 in the crumpled
phase. We should note that a possibility of a continuous transition is not
completely eliminated.Comment: 15 pages with 10 figure
Free boson formulation of boundary states in W_3 minimal models and the critical Potts model
We develop a Coulomb gas formalism for boundary conformal field theory having
a symmetry and illustrate its operation using the three state Potts model.
We find that there are free-field representations for six conserving
boundary states, which yield the fixed and mixed physical boundary conditions,
and two violating boundary states which yield the free and new boundary
conditions. Other violating boundary states can be constructed but they
decouple from the rest of the theory. Thus we have a complete free-field
realization of the known boundary states of the three state Potts model. We
then use the formalism to calculate boundary correlation functions in various
cases. We find that the conformal blocks arising when the two point function of
is calculated in the presence of free and new boundary conditions
are indeed the last two solutions of the sixth order differential equation
generated by the singular vector.Comment: 25 page
Mapping urban green infrastructure : a novel landscape-based approach to incorporating land-use and land-cover in the mapping of human-dominated systems
Common approaches to mapping green infrastructure in urbanized landscapes invariably focus on measures of land-use or land-cover and associated functional or physical traits. However, such one-dimensional perspectives do not accurately capture the character and complexity of the landscapes in which urban inhabitants live. The new approach presented in this paper demonstrates how open-source, high spatial and temporal resolution data with global coverage can be used to measure and represent the landscape qualities of urban environments. Through going beyond simple metrics of quantity, such as percentage green and blue cover it is now possible to explore the extent to which landscape quality helps to unpick the mixed evidence presented in the literature on the benefits of urban nature to human well-being. Here we present a landscape approach, employing remote sensing, GIS and data reduction techniques, to map urban green infrastructure elements in a large UK city-region. Comparison with existing urban datasets demonstrates considerable improvement in terms of coverage and thematic detail. The characterisation of landscapes, using census tracts as spatial units, and subsequent exploration of associations with social-ecological attributes highlights the further detail which can be uncovered with the approach. For example, eight urban landscape types identified for the case study city exhibited associations with distinct socio-economic conditions accountable not only to quantities but also qualities of green and blue space. The identification of individual landscape features through simultaneous measures of land-use and land cover demonstrated unique and significant associations between the former and indicators of human health and ecological condition. The approach may therefore provide a promising basis for developing further insight into the processes and characteristics which affect human health and wellbeing in urban areas, both in the UK and beyond
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