Generation and delivery of free hydroxyl radicals using a remote plasma

We demonstrate a new gas-based generation source using a low power radio frequency driven atmospheric pressure plasma configured to deliver the radical flux into the far effluent region, well away from interference from other plasma factors such as electric fields, currents, and ultraviolet radiation. Using He–H2O gas chemistry isolated from the laboratory air, the plasma generated flux contains and other radicals including, O and HO2 as well as H2O2 which, along with, was found to vary with H2O vapour content and absorbed power density. Peak flux values were 2.3 nmol s−1 and 0.23 nmol s1 for H2O2 and respectively at a distance of 50 mm from the plasma, with 790 ppmv H2O and a power density of ∼108 W m−3. The maximum flux density was 4.5 × 1019 m−2s−1 falling to 1.7 × 1019 m2 s1 at 110 mm, equivalent to generation rates of 74 µM s1 and 28 µM s−1. Despite high recombination rates at the plasma exit, the escaping flux is still significant, indicating a viable delivery capability to downstream targets. Its performance with regard to generation rates compares well with traditional generation techniques such as radiolysis, advanced oxidation processes and enhanced Fenton-chemistry approaches where production rates are sub-µM s−1. Delivering precisely quantifiable fluxes provides new opportunities for scientific studies and technological opportunities in cell biology, atmospheric chemistry, protein unfolding and systematic dose studies for plasma-based and other related potential medical treatments

Transparency ethics in practice: Revisiting financial conflicts of interest disclosure forms in clinical practice guidelines

Background Authors of clinical practice guidelines (CPGs) disclose financial conflicts of interest (FCOIs) to promote transparency ethics. Typically, they do so on standard declaration forms containing generic open-ended questions on FCOIs. Yet, the literature is scant on the format and effect of alternative disclosure forms. Does supplementing a standard form with subsequent detailed disclosure forms tailored to the context of the CPG improve the yield or accuracy of FCOIs declarations? Methods For an international CPG in gastroenterology on the endoscopic surveillance for colorectal neoplasia in inflammatory bowel disease, we compared the use of a standard FCOIs disclosure form with a contextual FCOIs disclosure form that detailed commercial relations related to the CPG topic. This included manufacturers of endoscopes, endoscopy equipment and accessories. Participants completed the generic form early, and the supplementary contextual form six months later. We then compared the FCOI disclosures obtained. Findings 26 participants provided FCOIs disclosures using both disclosure forms. We found discrepancies regarding (1) the disclosure of FCOIs (presence/absence), and (2) the listing of financial entities. While the number of participants who disclosed a FCOI remained the same (30.8%) using the two forms, disclosures were not from the same individuals: two additional participants disclosed a FCOI, whereas two participants withdrew previous disclosures. Among those who reported a FCOI in either form, we noted inconsistencies in disclosures for 70% of the participants. This included changes in FCOIs disclosure status or modifications of "their commercial relations". Discussion Accurate reporting of FCOIs advances the transparency and ethical integrity of CPGs. Our experience suggests that a contextual FCOIs disclosure form tailored to content of the CPG with narrow, detailed questions provides supplementary, more complete FCOIs declarations than generic forms alone. The finding raises challenges on how forms are best written and formatted, optimally timed, and more effectively processed with sensitivity to professional behaviour, so as to heighten transparency

The global impact of household contact management for children on multidrug-resistant and rifampicin-resistant tuberculosis cases, deaths, and health-system costs in 2019: a modelling study

Background: Estimates suggest that at least 30 000 children develop multidrug-resistant or rifampicin-resistant tuberculosis each year. Despite household contact management (HCM) being widely recommended, it is rarely done. Methods: We used mathematical modelling to evaluate the potential country-level and global effects and cost-effectiveness of multidrug-resistant or rifampicin-resistant tuberculosis HCM for children younger than 15 years who are living with a person with newly diagnosed multidrug-resistant or rifampicin-resistant tuberculosis. We compared a baseline of no HCM with several HCM strategies and tuberculosis preventive therapy regimens, calculating the effect on multidrug-resistant or rifampicin-resistant tuberculosis cases, deaths, and health-system costs. All HCM strategies involved the screening of children for prevalent tuberculosis disease but with tuberculosis preventive therapy either not given or targeted dependent on age, HIV status, and result of tuberculin skin test. We evaluated the use of fluoroquinolones (ie, levofloxacin and moxifloxacin), delamanid, and bedaquiline as tuberculosis preventive therapy. Findings: Compared with a baseline without HCM, HCM for all adults diagnosed with multidrug-resistant or rifampicin-resistant tuberculosis in 2019 would have entailed screening 227 000 children (95% uncertainty interval [UI]: 205 000–252 000) younger than 15 years globally, and averted 2350 tuberculosis deaths (1940–2790), costing an additional US$63 million (74–95 million). If all the children within the household who had been in contact with the person with multidrug-resistant or rifampicin-resistant tuberculosis received tuberculosis preventive therapy with levofloxacin, 5620 incident tuberculosis cases (95% UI 4540–6890) and an additional 1240 deaths (970–1540) would have been prevented. Incremental cost-effectiveness ratios were lower than half of per-capita gross domestic product for most interventions in most countries. Targeting only children younger than 5 years and those living with HIV reduced the number of incident cases and deaths averted, but improved cost-effectiveness. Tuberculosis preventive therapy with delamanid increased the effect, in terms of reduced incidence and mortality, compared with levofloxacin. Interpretation: HCM for patients with multidrug-resistant or rifampicin-resistant tuberculosis is cost-effective in most settings and could avert a substantial proportion of multidrug-resistant or rifampicin-resistant tuberculosis cases and deaths in children globally. Funding: UK Medical Research Council

Biallelic GINS2 variant p.(Arg114Leu) causes Meier-Gorlin syndrome with craniosynostosis

Contains fulltext : 284813.pdf (Publisher’s version ) (Open Access)INTRODUCTION: Replication of the nuclear genome is an essential step for cell division. Pathogenic variants in genes coding for highly conserved components of the DNA replication machinery cause Meier-Gorlin syndrome (MGORS). OBJECTIVE: Identification of novel genes associated with MGORS. METHODS: Exome sequencing was performed to investigate the genotype of an individual presenting with prenatal and postnatal growth restriction, a craniofacial gestalt of MGORS and coronal craniosynostosis. The analysis of the candidate variants employed bioinformatic tools, in silico structural protein analysis and modelling in budding yeast. RESULTS: A novel homozygous missense variant NM_016095.2:c.341G>T, p.(Arg114Leu), in GINS2 was identified. Both non-consanguineous healthy parents carried this variant. Bioinformatic analysis supports its classification as pathogenic. Functional analyses using yeast showed that this variant increases sensitivity to nicotinamide, a compound that interferes with DNA replication processes. The phylogenetically highly conserved residue p.Arg114 localises at the docking site of CDC45 and MCM5 at GINS2. Moreover, the missense change possibly disrupts the effective interaction between the GINS complex and CDC45, which is necessary for the CMG helicase complex (Cdc45/MCM2-7/GINS) to accurately operate. Interestingly, our patient's phenotype is strikingly similar to the phenotype of patients with CDC45-related MGORS, particularly those with craniosynostosis, mild short stature and patellar hypoplasia. CONCLUSION: GINS2 is a new disease-associated gene, expanding the genetic aetiology of MGORS

Manipulating Ferroelectric Domains in Nanostructures Under Electron Beams

Freestanding BaTiO3 nanodots exhibit domain structures characterized by distinct quadrants of ferroelastic 90{\deg} domains in transmission electron microscopy (TEM) observations. These differ significantly from flux-closure domain patterns in the same systems imaged by piezoresponse force microscopy. Based upon a series of phase field simulations of BaTiO3 nanodots, we suggest that the TEM patterns result from a radial electric field arising from electron beam charging of the nanodot. For sufficiently large charging, this converts flux-closure domain patterns to quadrant patterns with radial net polarizations. Not only does this explain the puzzling patterns that have been observed in TEM studies of ferroelectric nanodots, but also suggests how to manipulate ferroelectric domain patterns via electron beams.Comment: 5 pages, 6 figure

Western Isles Ferry fares mechanism study: a report for Conhairle nan Eilean Siar.

The study assessed the ferry operation under the existing fare structure and identified potential fare and operational models that could be applied or adapted to the Western Isles ferry routes. Recommendations were made on the most effective ferry fare mechanism and operational models for stimulating economic growth and social stability in the Western Isles

Western Isles Ferry fares mechanism study: a report for Conhairle nan Eilean Siar.

The study assessed the ferry operation under the existing fare structure and identified potential fare and operational models that could be applied or adapted to the Western Isles ferry routes. Recommendations were made on the most effective ferry fare mechanism and operational models for stimulating economic growth and social stability in the Western Isles

Using candidacy theory to explore unemployed over-50s perceptions of suitability of a welfare to work programme: a longitudinal qualitative study

Welfare to work interventions seek to move out‐of‐work individuals from claiming unemployment benefits towards paid work. However, previous research has highlighted that for over‐50s, particularly those with chronic health conditions, participation in such activities are less likely to result in a return to work. Using longitudinal semi‐structured interviews, we followed 26 over‐50s during their experience of a mandated welfare to work intervention (the Work Programme) in the United Kingdom. Focusing on their perception of suitability, we utilise and adapt Candidacy Theory to explore how previous experiences of work, health, and interaction with staff (both in the intervention, and with healthcare practitioners) influence these perceptions. Despite many participants acknowledging the benefit of work, many described a pessimism regarding their own ability to return to work in the future, and therefore their lack of suitability for this intervention. This was particularly felt by those with chronic health conditions, who reflected on difficulties with managing their conditions (e.g., attending appointments, adhering to treatment regimens). By adapting Candidacy Theory, we highlighted the ways that mandatory intervention was navigated by all the participants, and how some discussed attempts to remove themselves from this intervention. We also discuss the role played by decision makers such as employment‐support staff and healthcare practitioners in supporting or contesting these feelings. Findings suggest that greater effort is required by policy makers to understand the lived experience of chronic illness in terms of ability to RTW, and the importance of inter‐agency work in shaping perceptions of those involved

Asthma routinization, family asthma management, caregiver depressive symptoms, and medication adherence in Head Start preschool children

IntroductionMedication adherence is suboptimal in childhood asthma. Children rely on caregivers to manage medication administration. It is important to detect families who are at risk for poor adherence or to identify potential areas that can assist families with better adherence to asthma medications in order to improve asthma outcomes. We investigated the association between asthma routines, family asthma management knowledge and skills, and caregiver depressive symptoms with daily controller medication adherence among Head Start preschool children in Baltimore City.MethodsOur study included 256 low-income urban preschool children who were prescribed a daily controller medication. Asthma routinization (by the Asthma Routines Questionnaire), family asthma management [by the Family Asthma Management System Scale (FAMSS)], and caregiver depressive symptoms (by the Center for Epidemiological Studies – Depression) were assessed at baseline. The medication possession ratio (MPR) to measure adherence to daily controller medications was calculated at baseline and 12 months from pharmacy fill records. Multiple regression models evaluated the relationship between asthma routinization, the FAMSS, the CES-D, and MPR.ResultsResults indicated that only 7% of families had an MPR above 80% at baseline, and 24% of caregivers had clinically significant depressive symptoms. Higher asthma medication routines were associated with higher MPR at baseline (b = 0.05, p = 0.03). Higher family asthma management was associated with higher MPR at both baseline (b = 0.04, p < 0.01) and 12 months (b = 0.05, p < 0.01).DiscussionOur findings highlight the importance of family asthma management and maintaining medication routines over time to improve asthma controller medication adherence

Airborne measurements of trace gases and aerosols over the London metropolitan region

The Emissions around the M25 motorway (EM25) campaign took place over the megacity of London in the United Kingdom in June 2009 with the aim of characterising trace gas and aerosol composition and properties entering and emitted from the urban region. It featured two mobile platforms, the UK BAe-146 Facility for Airborne Atmospheric Measurements (FAAM) research aircraft and a ground-based mobile lidar van, both travelling in circuits around London, roughly following the path of the M25 motorway circling the city. We present an overview of findings from the project, which took place during typical UK summertime pollution conditions. Emission ratios of volatile organic compounds (VOCs) to acetylene and carbon monoxide emitted from the London region were consistent with measurements in and downwind of other large urban areas and indicated traffic and associated fuel evaporation were major sources. Sub-micron aerosol composition was dominated by secondary species including sulphate (24% of sub-micron mass in the London plume and 29% in the non-plume regional aerosol), nitrate (24% plume; 20% regional) and organic aerosol (29% plume; 31% regional). The primary sub-micron aerosol emissions from London were minor compared to the larger regional background, with only limited increases in aerosol mass in the urban plume compared to the background (~12% mass increase on average). Black carbon mass was the major exception and more than doubled in the urban plume, leading to a decrease in the single scattering albedo from 0.91 in the regional aerosol to 0.86 in the London plume, on average. Our observations indicated that regional aerosol plays a major role on aerosol concentrations around London, at least during typical summertime conditions, meaning future efforts to reduce PM levels in London must account for regional as well as local aerosol sources