Queen's University Belfast

About: Queen's University Belfast is a education organization based out in Belfast, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 25457 authors who have published 55463 publications receiving 1751346 citations. The organization is also known as: Queen's College, Belfast & Queen's College.

Ascertainment of Cause-Specific Mortality in COPD -- Operations of the TORCH Clinical Endpoint Committee

Abstract: Background: TORCH (Towards a Revolution in COPD Health) is an international multicentre, randomised, placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease (COPD). The primary outcome is all-cause mortality. Cause-specific mortality and deaths related to COPD are additional outcome measures, but systematic methods for ascertainment of these outcomes have not previously been described. Methods: A Clinical Endpoint Committee (CEC) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic, unbiased and independent manner. The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD-relatedness; the independent review of cases by all members with development of a consensus opinion; and a substantial infrastructure to collect medical information. Results: 911 deaths were reviewed and consensus was reached in all. Cause-specific mortality was: cardiovascular 27%, respiratory 35%, cancer 21%, other 10% and unknown 8%. 40% of deaths were definitely or probably related to COPD. Adjudications were identical in 83% of blindly re-adjudicated cases (κ = 0.80). COPD-relatedness was reproduced 84% of the time (κ = 0.73). The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52% of cases. Conclusion: A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.

Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease

Abstract: We identify the SLC22A3-LPAL2-LPA gene cluster as a strong susceptibility locus for coronary artery disease (CAD) through a genome-wide haplotype association (GWHA) study. This locus was not identified from previous genome-wide association (GWA) studies focused on univariate analyses of SNPs. The proposed approach may have wide utility for analyzing GWA data for other complex traits.

Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis.

Abstract: Familial expansile osteolysis (FEO, MIM 174810) is a rare, autosomal dominant bone disorder characterized by focal areas of increased bone remodelling. The osteolytic lesions, which develop usually in the long bones during early adulthood, show increased osteoblast and osteoclast activity. Our previous linkage studies mapped the gene responsible for FEO to an interval of less than 5 cM between D18S64 and D18S51 on chromosome 18q21.2-21.3 in a large Northern Irish family. The gene encoding receptor activator of nuclear factor-kappa B (RANK; ref. 5), TNFRSF11A, maps to this region. RANK is essential in osteoclast formation. We identified two heterozygous insertion mutations in exon 1 of TNFRSF11A in affected members of four families with FEO or familial Paget disease of bone (PDB). One was a duplication of 18 bases and the other a duplication of 27 bases, both of which affected the signal peptide region of the RANK molecule. Expression of recombinant forms of the mutant RANK proteins revealed perturbations in expression levels and lack of normal cleavage of the signal peptide. Both mutations caused an increase in RANK-mediated nuclear factor-kappaB (NF-kappaB) signalling in vitro, consistent with the presence of an activating mutation.

"Transfer cells": plant cells with wall ingrowths, specialized in relation to short distance transport of solutes - their occurrence, structure, and development

Abstract: Plant cells possessing ingrowths of wall material, and hence having protoplasts with unusually high surface-to-volume ratios, may be found in a wide variety of anatomical situations and in most of the major taxa of multicellular plants. They are termed here “transfer cells”. Their function relates to any of four categories of trans membrane flux: 1. Absorption of solutes from the external environment (e.g. epidermis of submerged leaves), 2. Secretion of solutes to the external environment (e.g. nectaries and other glands), 3. Absorption of solutes from an internal, extracytoplasmic compartment (e.g. vascular parenchyma, haustorial-type connections, embryo sacs and embryos), 4. Secretion of solutes into an internal extracytoplasmic compartment (e.g. tapetum of anther, pericycle of root nodule). An overall assessment of their occurrence, structure, development and role in the plant is presented taking account of published information and new observations.