Structure‐Function Relationships of Rhamnolipid and Exopolysacharide Biosurfactants of Pseudomonas aeruginosa as Therapeutic Targets in Cystic Fibrosis Lung Infections

Chronic Pseudomonas aeruginosa lung infection is the cause of much morbidity and most of the mortality in cystic fibrosis (CF) patients. The high prevalence of P. aeruginosa infections in CF is related to the microbe\u27s large genome and mechanisms of adaptation to the CF lung environment, the host immune system and antibiotic resistance. Among a wide range of P. aeruginosa metabolites involved in infection development in CF, the biosurfactant compounds, rhamnolipids (RLs) and exopolysaccharides (EPSs), have important roles in the early stages of P. aeruginosa infection in CF. RLs and EPSs are involved in bacterial adhesion, biofilm formation, antibiotic resistance, and impairment of host immune system pathways, as well as in processes such as biofilm maintenance and the mucoid phenotype of P. aeruginosa, which lead to development of chronic infection. Due to the proposed roles of RLs and EPSs and the importance of prevention and treatment of P. aeruginosa respiratory infections in CF, these compounds are promising targets for patient therapy. In the future, impairment of P. aeruginosa quorum sensing (QS) pathways and modification of host respiratory mucus epithelial membranes should be considered as potential approaches in preventing respiratory infections caused by this microbe in CF patients

Integrated Hepatitis C Care for People Who Inject Drugs (Heplink): Protocol for a Feasibility Study in Primary Care (Preprint)

Background: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and death. Drug use remains the significant cause of new infections in the European Union, with estimates of HCV antibody prevalence among people who inject drugs ranging from 5% to 90% in 29 European countries. In Ireland and the European Union, primary care is a key area to focus efforts to enhance HCV diagnosis and treatment among people who inject drugs. Objective: The Heplink study aims to improve HCV care outcomes among opiate substitution therapy (OST) patients in general practice by developing an integrated model of HCV care and evaluating its feasibility, acceptability, and likely efficacy. Methods: The integrated model of care comprises education of community practitioners, outreach of an HCV-trained nurse into general practitioner (GP) practices, and enhanced access of patients to community-based evaluation of their HCV disease (including a novel approach to diagnosis, that is, Echosens FibroScan Mini 430). A total of 24 OST-prescribing GP practices were recruited from the professional networks and databases of members of the research consortium. Patients were eligible if they are aged ≥18 years, on OST, and attend the practice for any reason during the recruitment period. Baseline data on HCV care processes and outcomes were extracted from the clinical records of participating patients. Results: This study is ongoing and has the potential to make an important impact on patient care and provide high-quality evidence to help GPs make important decisions on HCV testing and onward referral. Conclusions: A substantial proportion of HCV-positive patients on OST in general practice are not engaged with specialist hospital services but qualify for direct-acting antiviral drugs treatment. The Heplink model has the potential to reduce HCV-related morbidity and mortality. Registered Report Identifier: RR1-10.2196/904

HEPCARE EUROPE- A Case study of a Service Innovation Project Aiming at Improving the Elimination of HCV in Vulnerable Populations in Four European Cities

OBJECTIVES: Hepatitis C Virus (HCV) is an important cause of chronic liver disease. Among at-risk populations, access to diagnosis and treatment is challenging. We describe an integrated model of care, Hepcare Europe, developed to address this challenge. METHODS: Using a case-study approach, we describe the cascade of care outcomes at all sites. Costing analyses estimated the cost per person screened and linked to care. RESULTS: A total of 2608 participants were recruited across 218 clinical sites. HCV antibody test results were obtained for 2568(98.5%), 1074(41.8%) were antibody-positive, 687(60.5%) tested positive for HCV-RNA, 650(60.5%) were linked to care and 319(43.5%) started treatment. 196(61.4%) of treatment initiates achieved a Sustained Viral Response (SVR) at dataset closure, 108(33.9%) were still on treatment, 8(2.7%) defaulted from treatment, and 7(2.6%) had a virologic failure or died. The cost per person screened varied from Є194 to Є635, while cost per person linked to care varied from Є364 to Є2035. CONCLUSIONS: Hepcare enhanced access to HCV treatment and cure, costs were affordable in all settings, offering a framework for scale-up and reproducibility

Effect of Weld Schedule on the Residual Stress Distribution of Boron Steel Spot Welds

Press-hardened boron steel has been utilized in anti-intrusion systems in automobiles, providing high strength and weight-saving potential through gage reduction. Boron steel spot welds exhibit a soft heat-affected zone which is surrounded by a hard nugget and outlying base material. This soft zone reduces the strength of the weld and makes it susceptible to failure. Additionally, different welding regimes lead to significantly different hardness distributions, making failure prediction difficult. Boron steel sheets, welded with fixed and adaptive schedules, were characterized. These are the first experimentally determined residual stress distributions for boron steel resistance spot welds which have been reported. Residual strains were measured using neutron diffraction, and the hardness distributions were measured on the same welds. Additionally, similar measurements were performed on spot welded DP600 steel as a reference material. A correspondence between residual stress and hardness profiles was observed for all welds. A significant difference in material properties was observed between the fixed schedule and adaptively welded boron steel samples, which could potentially lead to a difference in failure loads between the two boron steel welds

Characterization of Loading Responses and Failure Loci of a Boron Steel Spot Weld

Boron steel, classed as an ultra high-strength steel (UHSS), has been utilized in anti-intrusion systems in automobiles, providing high strength and weight-saving potential through gage reduction. UHSS spot welds exhibit unique hardness distributions, with a hard nugget and outlying base material, but with a soft heat-affected zone in-between these regions. This soft zone reduces the strength of the weld and makes it susceptible to failure. Due to the interaction of various weld zones that occurs during loading, there is a need to characterize the loading response of the weld for accurate failure predictions. The loading response of certain weld zones, as well as failure loci, was obtained through physical simulation of the welding process. The results showed a significant difference in mechanical behavior through the weld length. An important result is that instrumented indentation was shown to be a valid, quantitative method for verifying the accuracy with which weld microstructure has been recreated with regard to the target weld microstructure