151398 research outputs found
Sort by
Visual loss in geographic atrophy: learnings from the lampalizumab trials
No full textPurposeTo assess the correlation of lesion growth rate and baseline factors, including foveal involvement and focality, on visual loss as measured by best-corrected visual acuity (BCVA) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).DesignRetrospective analysis of the lampalizumab phase 3 (NCT02247479 and NCT02247531) and prospective observational (NCT02479386) trials.ParticipantsPatients with bilateral GA.MethodsMonthly BCVA and fundus autofluorescence (FAF) at baseline and every 6 months for 2 years were analyzed. Baseline GA area from FAF images was correlated to baseline BCVA and change in BCVA. The lesion growth rate was calculated as the slope of a linear fit from all available GA area measurements of a patient. The association between GA growth rate quartiles and BCVA changes was assessed, subgrouped by GA foveal involvement or focality. Time-to-event analysis for BCVA loss of ≥5, ≥10, and ≥15 letters was performed. A Cox regression model adjusted for baseline factors was performed on these outcomes. Kaplan–Meier curves are provided for each baseline factor and GA growth rate.Main Outcome MeasuresCorrelations of baseline BCVA, GA area, and growth rate with change in BCVA, and time to ≥5, ≥10, and ≥15-letter loss by foveal involvement or focality.ResultsBest-corrected visual acuity and GA area at baseline did not correlate with BCVA change at any visit. Geographic atrophy growth rate showed a weak correlation with BCVA loss, which increased over time. The 2 highest GA growth rate quartiles had accelerated BCVA loss in eyes with subfoveal, unifocal lesions. Approximately 75%, 50%, and 25% of study eyes experienced a ≥5-, ≥10-, and ≥15-letter loss by 2 years, respectively.ConclusionsBest-corrected visual acuity and GA area at baseline did not correlate with BCVA loss, but faster GA growth rates appeared to be associated with faster BCVA loss. Geographic atrophy foveal involvement and focality correlated with the rate of BCVA loss with subfoveal lesions at high risk of vision loss over time, especially when the GA lesion was unifocal.<br/
Exploring the carbon footprint of severe asthma and change after biologic therapy initiation: an analysis of Northern Irish data
No full textBackgroundThe carbon footprint of severe asthma and the impact of biologic therapy in this population is unknown.MethodsThis was a retrospective cohort study in adults with severe asthma, using data from the Northern Ireland Regional Severe Asthma Service (September 2015–November 2021). We calculated annual greenhouse gas (GHG) emissions (carbon dioxide equivalent) for asthma-related medications and healthcare resource utilisation, compared patient characteristics by GHG quartile, calculated GHG change post-biologic initiation, and explored the relationship between GHG change and clinical response.ResultsAmong 303 patients with severe asthma, mean±sd GHG emissions were 474±431 kg, largely driven by SABA use (50.7%) and emergency department (ED) visits/inpatient admissions (21.0%). Those with highest-quartile GHG emissions were more likely to have uncontrolled disease (Asthma Control Questionnaire-5 score 3.5 versus 2.5; p<0.001), be more deprived (46.1% versus 25.0%; p=0.029) and have depression/anxiety (35.5% versus 14.7%; p=0.002) versus those with lowest-quartile GHG emissions. Among patients who received a biologic (n=213), modest GHG reductions (−28.0±286 kg; p=0.15) were observed, largely driven by a reduction in ED/hospitalisation-related GHG emissions (−59.3±224 kg; p<0.001). SABA-related GHG emissions were relatively unchanged (−6.1±138 kg; p=0.518). Total GHG emissions were 72.4±352 kg (p=0.044) lower than baseline at 4 years post-biologic initiation. Although there was substantial clinical improvement post-biologic initiation, this was not associated with GHG reductions.ConclusionsSevere asthma is associated with substantial GHG emissions, primarily driven by SABA use and emergency care utilisation. Although GHG emissions were lower post-biologic, largely due to a reduction in emergency care, the changes in GHG emissions were modest and SABA use was relatively unchanged. An improved understanding of the factors driving elevated GHG emissions is required.<br/
Enhancing 3D-printed chocolate drug delivery: the role of soy lecithin in improving formulation printability and consistency
No full textObjectivesThis study explores the potential of extrusion-based 3D printing to improve medication adherence by developing chocolate-based oral dosage forms incorporating active pharmaceutical ingredients such as paracetamol and ibuprofen while using soy lecithin as an emulsifier to enhance the flow properties of the chocolate formulation, enabling consistent and reliable 3D printing of the dosage forms.MethodsExtrusion-based 3D printing was used to obtain drug-loaded solid oral dosage forms. The formulation components as well as the printing design and conditions were optimized, to enhance the appearance and patient acceptability of the final products. Techniques such as spectroscopy, thermal analysis, rheology, mechanical analysis, and in-vitro dissolution were employed to assess the physicochemical properties of these formulations.Key findingsSoy lecithin was essential in obtaining robust and consistent dosage forms. The formulations showed good physicochemical stability of the components and demonstrated consistent drug release.ConclusionsThe findings suggest that extrusion-based 3D printing, with the aid of emulsifiers such as soy lecithin, is a viable method for producing personalized, chocolate-based drug delivery systems, potentially improving adherence through customizable dosage forms. Further research could enhance understanding of factors such as particle size, crystallinity, and the impact of chewing on drug release to optimize therapeutic outcomes.<br/
Sectoral coupling pathway towards a 100% renewable energy system for Northern Ireland
No full textNorthern Ireland, in alignment with the United Kingdom's net zero targets for 2050, is focusing on a transition to a 100 % renewable energy system. Wind energy is the backbone of this future system due to its abundant resource potential, low environmental impact, and cost-effectiveness. However, achieving a fully variable renewable energy system requires flexibility on the demand side to reliably facilitate the displacement of traditional dispatchable power plants with variable renewable resources such as wind and solar. To address this challenge, this study aims to develop optimal pathways for transitioning Northern Ireland's current energy system to 100 % renewable energy. The proposed model outlines eight pathway steps that reflect technical and operational changes needed on both the supply and demand sides. These steps include: 1) building a reference model, 2) implementing a district heating system, 3) deploying electric heat pumps, 4) reducing reliance on dispatchable power plants, 5) integrating electric vehicles, 6) incorporating demand-side management, 7) producing methanol for buses and trucks, and 8) replacing remaining fossil fuels with synthetic gas. Each step is evaluated using EnergyPLAN, which considers both technical and economic viability alongside the increased penetration of wind and solar power. The findings illustrate that Northern Ireland can transition to a 100 % renewable energy system at a cost comparable to its current system, providing a practical and cost-effective pathway to meet its 2050 target. By analysing the impact of each step individually, this study provides valuable insights for policymakers on effectively decarbonising Northern Ireland's entire energy system
Natural peptide as a kinetic promoter for methane hydrate formation: insights from experiments and molecular simulations
No full textThe influence of biomolecules on the kinetics of gas hydrate formation has received some attention in the scientific community. However, the underlying physicochemical mechanisms are still not well understood. Recently, a peptide present in a protein produced by a marine methylotrophic bacterium was found to promote methane hydrate formation under natural conditions. In this study, we take an in-depth look at the effect of this natural peptide on the formation of methane hydrates. Our research employed a dual methodology. Methane hydrates were formed experimentally under high-pressure conditions to study the formation kinetics, while molecular dynamics simulations were carried out to reveal the mechanisms at the nanoscale. Our results confirm that the natural peptide acts as a kinetic promoter for hydrate formation at an environmentally relevant concentration of Image 1 . We argue that this effect is achieved by a stabilization of the nascent hydrate nuclei, via adsorption of the peptide at their surface. Our study highlights the role of each amino acid in the peptide sequence, and thus provides valuable insights into the design of efficient and sustainable promoters. More fundamentally, it lays a solid foundation for our understanding of the interactions between marine microbial communities and methane hydrate deposits.<br/
Summary of working group 2: Laser-driven plasma acceleration of ions
No full textThis article summarizes contributions in WG2 (Laser-driven plasma acceleration of ions) made at AAC24. Topics include advancing the maximum proton energy beyond 100 MeV; repetition rate, innovative targets; and characterisation and improvement of shot-to-shot stability, beam quality, and conversion efficiency. Applications of interest for ion beams presented at AAC24 include radiobiology, materials science, fundamental physics, and fast-ignition inertial confinement fusion (ICF)
Eliminating ghost phantoms in computational microwave imaging by breaking receiver symmetry
No full textThis paper addresses the challenge of eliminating ghost phantoms in frequency-diverse computational microwave imaging (CMI) by optimizing the arrangement of receiving antennas. Ghost phantoms, usually refer to unreal objects that appear in reconstructed images, can cause significant challenges. These ghost phantoms are primarily attributed to factors such as system inaccuracies, deficiencies in signal processing and the intricate electromagnetic phenomena present in the environment. Traditional approaches to address this issue in CMI focus on enhancing signal processing algorithms or increasing the diversity of measurement modes. In this work, we present that the intrinsic symmetry in the arrangement of transmitter (Tx) and receiver (Rx) components of a CMI system also substantially contributes to the occurrence of these ghost phantoms in reconstructions. We propose a solution by breaking the symmetry in the Rx configuration to reduce the ghost phantom occurrence in the reconstructed images. We use full-wave simulations to investigate the effects of three different receiver arrangement schemes on image reconstruction: uniform, half-uniform and half-irregular, and fully irregular. The results demonstrate that breaking the symmetry of the Rx elements, particularly by adopting an irregular arrangement, significantly improves the quality of the reconstructed images.<br/
Microbial fuel cells to monitor natural attenuation around groundwater plumes
No full textThis research presents a straightforward and economically efficient design for a microbial fuel cell (MFC) that can be conveniently integrated into a borehole to monitor natural attenuation in groundwater. The design employs conventional, transparent, and reusable PVC bailers with graphite tape and granular activated carbon to create high surface area electrodes. These electrodes are connected across redox environments in nested boreholes through a wire and variable resistor setup. The amended electrodes were installed in pre-existing boreholes surrounding a groundwater plume near a former gasworks facility. Among all the MFC locations tested, the MFC at the plume fringe exhibited the highest electrical response and displayed significant variations in the differential abundance of key bacterial and archaeal taxa between the anode and cathode electrodes. The other MFC configurations in the plume center and uncontaminated groundwater showed little to no electrical response, suggesting minimal microbial activity. This straightforward approach enables informed decision-making regarding effectively monitoring, enhancing, or designing degradation strategies for groundwater plumes. It offers a valuable tool for understanding and managing contaminant degradation in such environments.<br/
Effect of posterior corneal surgically induced astigmatism on toric intraocular lens power calculations
No full textBackground: To determine whether accounting for posterior corneal surgically induced astigmatism (SIA) would improve toric intraocular lens power calculation prediction error.Methods: A total of 189 eyes of 148 patients undergoing routine cataract surgery were included in the study. Standard and posterior keratometry were measured pre- and postoperatively. Centroid SIA with standard keratometry and posterior keratometry were calculated separately. Prediction errors for postoperative refractive astigmatism at 4 weeks postoperatively were compared for Barrett Toric with predicted posterior corneal astigmatism (PPCA); Barrett Toric with preoperative measured posterior corneal astigmatism (MPCA); Barrett Toric with postoperative MPCA, which accounts for posterior corneal SIA.Results: There was a significant increase in PCA magnitude postoperatively (p < 0.001), although a change of > 0.3D occurred in only 3% of eyes. There was a postoperative rotation in the steep meridian of > 10° in 32% of eyes. The Barrett Toric formula with PPCA yielded a significantly smaller refractive astigmatism prediction error compared to when a postoperative MPCA value was used (p < 0.01). Postoperative MPCA had a lower proportion of eyes within 0.50, 0.75 and 1.00D of predicted refractive astigmatism than PPCA or preoperative MPCA, although this was not statistically significant.Conclusion: This study demonstrated postoperative changes in posterior corneal astigmatism magnitude and the orientation of the steep meridian. However, accounting for posterior keratometric SIA in the Barrett Toric formula does not improve refractive astigmatism prediction accuracy
The detoxome capacity of the adult rumen fluke Calicophoron daubneyi extends into its secreted extracellular vesicles
No full textHelminth parasites have long adapted to survive hostile host environments and can likely adapt against the chemical anthelmintic challenge. One proposed adaptation route is via Phase I and II xenobiotic metabolizing enzymes (XMEs). For successful Helminth pharmacotherapy discovery programs, a working understanding of Helminth-derived chemical detoxification, the Helminth detoxome, is a must. At present, the detoxome of a newly emerging Helminth parasite, the rumen fluke Calicophoron daubneyi, remains unexplored. Thus, a combined bioinformatics, sub-, and global-proteomic approach has been employed to examine the detoxome of adult C. daubneyi. Transcriptome analysis revealed a complement of Phase I (cytochrome P450s and monoamine oxygenases) and Phase II (glutathione transferases [GSTs] and sulfotransferases) XMEs. Affinity-led subproteomic exploration of the GSTs revealed six GST isoforms in adult rumen fluke (CdGST-Mu1-2, S1, and S3–5), with global approaches identifying additional GSTs (CdGST-O1-2, Z1, and S2) and a unique egg-specific variant (CdGST-S6). Examination of C. daubneyi extracellular vesicles revealed a GST profile replicating that of the adult with the absence of two isoforms (CdGST-S2 and S4), with an additional identification of a sulfotransferase. These data represent the first exploration into the complete rumen fluke detoxification capacity and will provide direction for future anthelmintic discovery programs