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1.
Br J Haematol ; 197(3): 310-319, 2022 05.
Article in English | MEDLINE | ID: mdl-35235680

ABSTRACT

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of solid-organ transplantation (SOT). We present the incidence and outcomes of PTLD in a cohort of 5365 SOT recipients over a 20-year period at two UK transplant centres. With a median follow-up of 7.7 years, 142 of 5365 patients have developed PTLD. Cumulative incidence was 18% at five years after multivisceral transplant and 1%-3% at five years following the other SOT types. Twenty-year cumulative incidence was 2%-3% following liver and heart transplantation and 10% following kidney transplantation. Median overall survival (OS) following SOT was 16 years, which is significantly reduced compared with the age-adjusted UK population. There is relatively high early mortality following diagnosis of PTLD and only patients surviving two years regained a longer-term survival approaching the non-PTLD SOT cohort. Of 90 patients with monomorphic PTLD, diffuse large B-cell lymphoma, 66 were treated with first-line rituximab monotherapy and 24 received first-line rituximab plus chemotherapy. Up-front rituximab monotherapy does not appear to compromise OS, but the number of patients dying from non-lymphoma causes before and after treatment remains high with both treatment approaches. Multivariate analysis of all 90 monomorphic PTLD patients identified an International Prognostic Index (IPI) of 3+ as the strongest pretreatment variable associating with inferior one-year OS.


Subject(s)
Epstein-Barr Virus Infections , Lymphoproliferative Disorders , Organ Transplantation , Epstein-Barr Virus Infections/complications , Humans , Incidence , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/epidemiology , Lymphoproliferative Disorders/etiology , Organ Transplantation/adverse effects , Retrospective Studies , Rituximab/therapeutic use , United Kingdom/epidemiology
2.
Proc Math Phys Eng Sci ; 474(2212): 20170639, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29740254

ABSTRACT

In textural equilibrium, partially molten materials minimize the total surface energy bound up in grain boundaries and grain-melt interfaces. Here, numerical calculations of such textural equilibrium geometries are presented for a space-filling tessellation of grains with a tetrakaidecahedral (truncated octahedral) unit cell. Two parameters determine the nature of the geometries: the porosity and the dihedral angle. A variety of distinct melt topologies occur for different combinations of these two parameters, and the boundaries between different topologies have been determined. For small dihedral angles, wetting of grain boundaries occurs once the porosity has exceeded 11%. An exhaustive account is given of the main properties of the geometries: their energy, pressure, mean curvature, contiguity and areas on cross sections and faces. Their effective permeabilities have been calculated, and demonstrate a transition between a quadratic variation with porosity at low porosities to a cubic variation at high porosities.

3.
Geochem Geophys Geosyst ; 19(12): 4694-4721, 2018 Dec.
Article in English | MEDLINE | ID: mdl-31007625

ABSTRACT

The observed variability of trace-element concentration in basaltic lavas and melt inclusions carries information about heterogeneity in the mantle. The difficulty is to disentangle the contributions of source heterogeneity (i.e., spatial variability of mantle composition before melting) and process heterogeneity (i.e., spatial and temporal variability in melt transport). Here we investigate the end-member hypothesis that variability arises due to source heterogeneity alone. We model the attenuation of trace-element variability introduced into the bottom of a one-dimensional, steady-state melting column. Our results show that the melting column can be considered to be a filter that attenuates variability according to the wavelength of heterogeneity, the partition coefficient of the trace element, melt productivity, and the efficiency of melt segregation. We further show that while the model can be fit to the observations, this requires assumptions inconsistent with constraints on the timescales of magma assembly. Hence, we falsify the end-member hypothesis and, instead, conclude that observed variability requires heterogeneity of melt transport. This might take the form of channels or waves and would almost certainly interact with source heterogeneity.

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