Waste materials have been used in concrete for many years, a typical example being fly ash from coal-fired power stations. The novel aspect of the concrete used in the work described in this presentation is that it is made entirely from industrial waste with no other materials except water. The resulting performance is not appropriate for use in typical structural applications but is well suited to waste containment.\nResearch in the nuclear industry has shown that cementitious materials offer many benefits for waste containment. Concrete has, however, not previously gained acceptance as a material for the construction of mineral liners because of concerns over high cost. This project exploits recent changes in the regulatory and economic environment to overcome these concerns.\nIn this presentation a programme to develop concrete landfill barriers will be described and the elements of the safety case for them will be presented. The safety case is based on predicting the transport of harmful species through the barrier. A model has been developed for the transport processes and, using data from laboratory tests, it has been validated against observations from site trials that have been in progress for the last five years.\nEach of the elements of the safety case will be introduced:\n- Laboratory tests for permeability, diffusion, adsorption and physical properties.\n- Site trials.\n- The computer model and validation of the model using the test cells and other codes.\n- Leaching from the barrier.\n- Long term chemical stability of the barrier itself.\n- Cracked samples.\n- Modelling transport in the new barrier and flow into the local environment.\n
Abstract Disclosure: S.S. Chugh: None. U.A. Khawaja: None. B.H. Barnes: Sanofi, Regeneron Pharmaceuticals. E.C. McGowan: Takeda, Bristol-Myers Squibb, AstraZeneca, Regeneron Pharmaceuticals, Sanofi. M. Misra: None. Background: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease characterized by eosinophil-predominant inflammation (≥15 eosinophils per high-power field) and esophageal dysfunction. It frequently coexists with atopic conditions, and has a male predominance. Chronic inflammation is known to impact bone health deleteriously in other conditions. The goal of this study was to evaluate the impact of EoE on bone mineral density (BMD) in pediatric and young adult patients, and to identify key risk factors associated with low BMD. Methods: This study was approved by our Institutional Review Board (IRB). A retrospective chart review was conducted for 123 patients with EoE, aged 5–25 years (98 males, 25 females), who underwent dual-energy X-ray absorptiometry (DXA) for BMD assessment. 103 patients were younger than 18 years, and 20 were 18 years or older. Data were collected from electronic medical records spanning January 2020, to January 2025 (60 months). Data management was performed using REDCap, and statistical analysis using JMP Pro 18.0.2. Results: Patients with EoE had a median age of 11.3 years (IQR: 9–16) and median disease duration of 47 months (IQR: 20–77). The median BMI was 19.0 (IQR: 17–22) kg/m2, and BMI z-score (BMIz) 0.48 (IQR: -0.54 to 1.34).Hip BMD Z-scores (n=76) had a median of -0.67 (IQR: -1.59 to 0.26), with 37% below -1 SD and 16% below -2 SD. Spine BMD Z-scores (n=105) had a median of -0.48 (IQR: -1.16 to 0.38), with 30% below -1 SD and 12% below -2 SD. Total body less head BMD Z-scores (n=44) had a median of -0.82 (IQR: -1.69 to 0.25), with 45% below -1 SD and 21% below -2 SD.In a multivariate model that included age, sex, BMIz, duration since diagnosis, and whether or not EoE had remitted, associations were identified of (i) hip BMD Z-scores with BMIz (p = 0.016), sex (p = 0.004) and age (p=0.004), (ii) spine BMD Z-scores with BMIz (p<0.0001), and (iii) total bod y less head BMD Z-scores with BMIz (p=0.004). 25OHD levels were not associated with BMD Z-scores.Males had lower BMD Z-scores than females at both the hip (p = 0.001) and spine (p = 0.021), underscoring sex-based differences in bone health. A larger proportion of males vs. females had a diagnosis of autism (18.4% vs. 4.0%, p=0.045), a known risk factor for low BMD, but a diagnosis of autism was not independently associated with BMD Z-scores. Conclusions: Patients with EoE exhibited a high prevalence of low BMD, particularly at the hip and spine, with significant sex-based differences. BMIz was the strongest predictor of BMD across all sites, and males had lower BMD than females. These findings emphasize the need for early BMD screening and targeted interventions to mitigate long-term skeletal risks in this population. Further research is warranted to explore the longitudinal impact of EoE-related factors on bone health and to develop preventive strategies. Presentation: Saturday, July 12, 2025
Background Numerous definitions for peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) and coronary bypass grafting (CABG) surgery exist. Objectives The purpose of this study was to investigate the PMI rates according to various definitions, their clinically relevant association with all-cause mortality at 10 years, and their impact on composite endpoints at 5 years in the SYNTAXES (Synergy between PCI with Taxus and Cardiac Surgery Extended Survival) trial. Methods PMI was classified as a myocardial infarction occurring within 48 h of the procedure according to definitions of the SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries), ISCHEMIA (International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches), and EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials; the Fourth Universal Definition of MI; and the Society for Cardiovascular Angiography and Interventions (SCAI). Of the 1,800 patients enrolled, 1,652 with creatine kinase and/or creatine kinase-myocardial band (CK-MB) post-procedure were included. The association between PMI and mortality was analyzed by Cox regression. Results PMI rates according to the SYNTAX and Fourth Universal Definition of MI, both of which required CK-MB elevation and electrocardiographic evidence of permanent myocardial damage, were 2.7% and 3.0%, respectively, in the PCI arm versus 2.4% and 2.1%, respectively, in the CABG arm. PMI rates according to the SCAI or EXCEL definition were higher in the PCI (5.7%) and CABG (16.5%) arms. PMIs according to the SYNTAX and Fourth Universal Definition of MI were more strongly associated with mortality than EXCEL and SCAI PMIs defined by isolated enzyme elevation when CK-MB was more than 10 times ULN. The impact of these “enzyme-driven events” on time-to-event curves and the composite endpoints was greater in the surgical cohort. PMIs after PCI were associated with 10-year mortality regardless of definition, whereas their impact on mortality after CABG was limited to 1 year. Conclusions The rates of PMI are highly dependent on their definition, which affects time-to-event curves, composite endpoints, and their lethal prognostic relevance. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)
No abstract is provided for this article.
DEP increase hospitalisation of patients with COPD. DEP comprise a carbon core with adsorbed compounds, including endotoxin. DEP deposit in the lungs, and are targets for macrophages. Macrophages drive COPD pathophysiology by releasing inflammatory mediators, potentially via mitogen-activated protein kinase (MAPK) pathways. We hypothesised that DEP stimulate macrophage mediator release via MAPK, and this is increased in COPD. MDM from non-smokers, smokers or COPD patients were treated with either DEP, standard reference material (SRM)-2975, SRM-1650b or inert beads (30, 11 and 0.2µm diameter, respectively) (1-100μg/ml) for 24h. CXCL8 release was analysed by ELISA, phagocytosis of fluorescent beads by fluorimetry, activation of MAPK by immunobloting, cell viability by MTT, and endotoxin levels by Limolas-amoebocyte lysate assay. DEP inhibited MDM phagocytosis of beads from all goups in a concentration-dependent manner, with 100μg/ml giving ∼60% inhibition (with ∼24% decrease in viability). DEP, but not SRMs or beads, stimulated CXCL8 release by MDM compared with non-stimulated controls (not due to the presence of endotoxin). MDM from non-smokers or COPD patients were twice as responsive to DEP than cells from smokers. DEP-treated MDM activated p38 and ERK 1/2 MAPK pathways, but not JNK. A p38 inhibitor (PF755616) suppressed DEP-treated MDM activation of p38 and CXCL8 release with no effect on viability. In conclusion, DEP, but not other particles, stimulated MDM chemokine release via p38 and ERK, suggesting that DEP composition drives this response and that p38 inhibition may have therapeutic potential in COPD.
There is conflicting evidence as to which autonomic receptors mast cells possess and whether the receptors are capable of modulating mediator release. We have studied dog mastocytoma cells because they are available in large numbers in a relatively pure form, unlike normal dog mast cells. Mastocytoma nodules from a dog were excised and disaggregated with collagenase to provide a cell suspension of mastocytoma cells of greater than 92% purity. The presence of autonomic receptors was assessed by both radioligand binding assays and by evaluating pharmacologic modulation of mediator release. In the radioligand binding assays, beta-adrenergic receptors were estimated by [3H]dihydroalprenolol binding, alpha-adrenergic receptors by [3H]prazosin binding and cholinergic receptors by [3H]quinuclidinyl benzilate binding. Nonspecific binding was determined in each case by incubation in the presence of the specific antagonists propranolol, phentolamine, and atropine, respectively. The effect of autonomic agonists on immunologic and nonimmunologic histamine release was examined, using the beta-adrenergic agonists isoproterenol and terbutaline, the alpha-adrenergic agonist phenylephrine with and without propranolol, and the cholinergic agonist acetylcholine. Dose-response curves were constructed both for the autonomic agonists and the histamine-releasing agents. Results from the radioligand binding and the pharmacologic studies were concordant. These dog mastocytoma cells had a high density of beta-receptors (21,500 +/- 3,300; mean +/- SE beta-receptors/cell, n=5) of which the predominant subtype appeared to be beta2. No evidence was found for the presence of alpha-adrenergic or cholinergic receptors either by direct receptor binding or by their actions on histamine release.
