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Antibody persistence following meningococcal ACWY conjugate vaccine licensed in the European Union by age group and vaccine
No full textIntroduction: Meningococcal disease caused by Neisseria meningitidis is a major cause of meningitis and septicaemia with high rates of morbidity and mortality worldwide. MenACWY-TT and MenACWY-CRM197 are meningococcal conjugate vaccines approved for use in children and adults in UK. The aim of this review was to evaluate and compare antibody responses and persistence in different age groups after MenACWY-TT and MenACWY-CRM197.Areas covered: Randomised trials showed that MenACWY-TT is immunogenic at all ages. MenACWY-CRM197 is immunogenic for infants and adults, but there is a lack of data for children aged 1 to 2 years. Studies on MenACWY-TT indicated that serum bactericidal antibody (SBA) utilising babby rabbit complement (rSBA) titres were significantly higher and more stable than SBA using human complement (hSBA) titres, compared with hSBA titres, which were lower and declined more rapidly by one year following post-primary MenACWY-TT and MenACWY-CRM197 vaccination, especially for MenA.Expert opinion: MenACWY-TT and MenACWY-CRM197 are both well tolerated and induce similar antibody persistence and immunogenicity against all four serogroups for individuals more than one year old. rSBA assay is a more robust assay than the hSBA assay when vaccinating with MenACWY-TT, while rSBA and hSBA assays had similar antibody persistence when vaccinating with MenACWY-CRM197
Observation of Hand Hygiene Practices in Home Health Care
No full textObjective: To describe nurse hand hygiene practices in the home health care setting (HHC), nurse adherence to hand hygiene guidelines, and factors associated with hand hygiene opportunities during home care visits.Design: Observational study of nurse hand hygiene practices.Setting and Participants: Licensed practical/vocational and registered nurses were observed in the homes of patients being served by a large non-profit HHC agency.Methods: Two researchers observed 400 home care visits conducted by 50 nurses. The World Health Organization’s “5 Moments for Hand Hygiene” validated observation tool was used to record opportunities and actual practices of hand hygiene, with three additional opportunities specific to the HHC setting. Patient assessment data available in the agency electronic health record and a nurse demographic questionnaire were also collected to describe patients and nurse participants.Results: A total of 2014 opportunities were observed. Upon arrival in the home was the most frequent opportunity (N=384), the least frequent was after touching a patient’s surroundings (N=43). The average hand hygiene adherence rate was 45.6% after adjusting for clustering at the nurse-level. Adherence was highest after contact with body fluid (65.1%); lowest after touching a patient (29.5%). The number of hand hygiene opportunities was higher when patients being served were at increased risk of an infection-related emergent department visit or hospitalization and when the home environment was observed to be “dirty”. No nurse or patient demographic characteristics were associated with the rate of nurse hand hygiene adherence.Conclusions and Implications: Hand hygiene adherence in HHC is suboptimal, with rates mirroring those reported in hospital and outpatient settings. The connection between poor hand hygiene and infection transmission has been well studied and it has received widespread attention with the outbreak of SARS-CoV-2. Agencies can use results found in this study to better inform quality improvement initiatives
Quantitative electro-reduction of CO2 to liquid fuel over electro-synthesised metal-organic frameworks
No full textOur Migration Story: History, the National Curriculum, and Re-Narrating the British Nation
No full textThis article explores schools as a key organisational context for the (re)production of national identity, and uses ongoing debates around the national curriculum for history, to illuminate the ongoing lacunae in Britain’s national memory. Taking the recent Windrush scandal as a starting point, we examine how these events reflect broader processes of historical forgetting in contemporary discussions around migration, empire and its loss. While this has been challenged by academic historians, there is a significant gap between these discourses and how history is taught in schools, which remain a key site for the transmission of a highly selective historical narrative/repertoire. We use the experience of the recent Our Migration Story project to consider alternative ways of thinking about Britain’s history, and to explore the importance of, and the difficulties in, challenging dominant memorialising practices
Simultaneous Ivabradine Parent-Metabolite PBPK/PD modelling using a Bayesian estimation method
No full textIvabradine and its metabolite both demonstrate heart rate reducing effect (If current inhibitors) and undergo CYP3A4 metabolism. The purpose of this study was to develop a joint parent-metabolite physiologically-based pharmacokinetic (PBPK)/ pharmacodynamic (PD) model to predict the PK and PD of ivabradine and its metabolite following intravenous (i.v.) or oral administration (alone or coadministered with CYP3A4 inhibitors). Firstly, a parent-metabolite disposition model was developed and optimised using individual plasma concentration-time data following i.v. administration of ivabradine or metabolite within a Bayesian framework. Secondly, the model was extended and combined with a mechanistic intestinal model to account for oral absorption and drug-drug interactions (DDIs) with CYP3A4 inhibitors (ketoconazole, grapefruit juice). Lastly, a PD model was linked to the PBPK model to relate parent and metabolite PK to heart rate (HR) reduction. The disposition model described successfully parent-metabolite PK following i.v. administration. Following integration of a gut model, the PBPK model adequately predicted plasma concentration profiles and the DDIs risk (92% and 86% of predicted AUC+inhibitor/AUCcontrol and Cmax+inhibitor/Cmaxcontrol for ivabradine and metabolite within the prediction limits). Ivabradine-metabolite PBPK model was linked to PD by using the simulated unbound parent-metabolite concentrations in the heart. This approach successfully predicted the effects of both entities on HR (observed vs predicted: -7.7/-5.9 bpm and -15.8/-14.0 bpm, control and ketoconazole group, respectively). This study provides a framework for PBPK/PD modelling of a parent-metabolite and can be scaled to other populations or used for investigation of untested scenarios (e.g. evaluation of DDI risk in special populations)
DEATHSTAR: Nearby AGB stars with the Atacama Compact Array I. CO envelope sizes and asymmetries:A new hope for accurate mass-loss-rate estimates
No full textContext. This is the first publication from the DEATHSTAR project. The overall goal of the project is to reduce the uncertainties of the observational estimates of mass-loss rates from evolved stars on the Asymptotic Giant Branch (AGB).Aims. The aim in this first publication is to constrain the sizes of the 12CO emitting region from the circumstellar envelopes around 42 mostly southern AGB stars, of which 21 are M-type and 21 are C-type, using the Atacama Compact Array (ACA) at the Atacama Large Millimeter/submillimeter Array (ALMA). The symmetry of the outflows is also investigated. Methods. Line emission from 12CO J=2→1 and 3→2 from all of the sources were mapped using the ACA. In this initial analysis, the emission distribution was fit to a Gaussian distribution in the uv-plane. A detailed radiative transfer analysis will be presented in a future publication. The major and minor axis of the best-fit Gaussian at the line center velocity of the 12CO J=2→1 emission givesa first indication of the size of the emitting region. Furthermore, the fitting results, such as the Gaussian major and minor axis, center position, and the goodness of fit across both lines, constrain the symmetry of the emission distribution. For a subsample of sources, the measured emission distribution is compared to predictions from previous best-fit radiative transfer modeling results.Results. We find that the CO envelope sizes are, in general, larger for C-type than for M-type AGB stars, which is as expected if the CO/H2 ratio is larger in C-type stars. Furthermore, the measurements show a relation between the measured (Gaussian) 12CO J=2→1 size and circumstellar density that, while in broad agreement with photodissociation calculations, reveals large scatter andsome systematic differences between the different stellar types. For lower mass-loss-rate irregular and semi-regular variables of both M- and C-type AGB stars, the 12CO J=2→1 size appears to be independent of the ratio of the mass-loss rate to outflow velocity, which is a measure of circumstellar density. For the higher mass-loss-rate Mira stars, the 12CO J=2→1 size clearly increases withcircumstellar density, with larger sizes for the higher CO-abundance C-type stars. The M-type stars appear to be consistently smaller than predicted from photodissociation theory. The majority of the sources have CO envelope sizes that are consistent with a spherically symmetric, smooth outflow, at least on larger scales. For about a third of the sources, indications of strong asymmetries are detected. This is consistent with what was found in previous interferometric investigations of northern sources. Smaller scale asymmetries arefound in a larger fraction of sources.Conclusions. These results for CO envelope radii and shapes can be used to constrain detailed radiative transfer modeling of the same stars so as to determine mass-loss rates that are independent of photodissociation models. For a large fraction of the sources, observations at higher spatial resolution will be necessary to deduce the nature and origin of the complex circumstellar dynamics revealed by our ACA observations
Natural attenuation of lead by microbial manganese oxides in a karst aquifer
No full textLead is a toxic environmental contaminant associated with current and historic mine sites. Here we studied the natural attenuation of Pb in a limestone cave system that receives drainage from the ancient Priddy Mineries, UK. Extensive deposits of manganese oxides were observed to be forming on the cave walls and as coatings in the stream beds. Analysis of these deposits identified them as birnessite (δ-MnO2), with some extremely high concentrations of sorbed Pb (up to 56 wt. %) also present. We hypothesised that these cave crusts were actively being formed by microbial Mn(II)-oxidation, and to investigate this the microbial communities were characterised by DNA sequencing, enrichment and isolation experiments. The birnessite deposits contained abundant and diverse prokaryotes and fungi, with ~5 % of prokaryotes and ~10 % of fungi closely related to known heterotrophic Mn(II)- oxidisers. A substantial proportion (up to 17 %) of prokaryote sequences were assigned to groups known as autotrophic ammonia and nitrite oxidisers, suggesting that nitrogen cycling may play an important role in contributing energy and carbon to the cave crust microbial communities and consequently the formation of Mn(IV)-oxides and Pb attenuation. Enrichment and isolation experiments showed that the birnessite deposits contained Mn(II)- oxidising microorganisms, and two isolates (Streptomyces sp. and Phyllobacterium sp.) could oxidise Mn(II) in the presence of 0.1 mM Pb. Supplying the enrichment cultures with acetate as a source of energy and carbon stimulated Mn(II)-oxidation, but excess organics in the form of glucose generated aqueous Mn(II), likely via microbial Mn(IV)-reduction. In this karst cave, microbial Mn(II)-oxidation contributes to the active sequestration and natural attenuation of Pb from contaminated waters, and therefore may be considered a natural analogue for the design of wastewater remediation systems and for understanding the geochemical controls on karst groundwater quality, a resource relied upon by billions of people across the glob
Research priorities in pediatric asthma: Results of a global survey of multiple stakeholder groups by the Pediatric Asthma in Real Life (PeARL) Think Tank
No full textBackground: Pediatric asthma remains a public health challenge with enormous impact worldwide. Objective: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, that could be used to guide future research and policy activities. Methods: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life (PeARL) Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers and the pharmaceutical industry). Differences across responder groups were compared. Results: 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions which highlight the importance of involving the whole range of stakeholders in formulation of recommendations. Conclusion: Different stakeholders agree in the majority of research and strategic (e.g. prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider
