Carbon Black Exposure Induces Alterations in Mitochondrial Morphology in Human Lung Cells: A Software-Based Quantitative Analysis

Nanoparticulates of pure carbon, carbon black (CB), are a common atmospheric pollutant in industrialized and heavily populated areas. They are produced primarily via combustion of fossil fuels, and represent a significant health hazard. They are known to worsen asthma and bronchitis when inhaled and to cause inflammation, heart dysfunction, and oxidative stress when incorporated into other organs. The key focal point of this work was to examine markers of stress signaling and cellular dysfunction when human bronchial epithelial cells (16HBE14o-) were exposed to CB particles ranging in size from 70 nm and averaging 130 nm in diameter. BrdU incorporation and DAPI staining studies revealed a 24-hour CB exposure (25 ug/ml and higher) to reduce rates of cell division and to significantly elevate percentages of cells exhibiting apoptotic nuclear morphology. Chronic exposure (24 days) of cells to low doses of CB (5 ug/ml) revealed a significant impact upon both cell division and survival. A central marker for stress signaling in these lung cells was elevation of reactive oxygen species, which rose within 12 hours of CB exposure, consistent with stress signals that induce mitochondrial apoptosis. Sirtuin 1, a stress regulated protein deacetylase in the cytosol, whose levels are known to be destabilized by ROS elevation in stressed cells, displayed no significant change following CB exposure at varied doses. Analysis of mitochondrial dynamics via fluorescence microscopy revealed clear changes in organization and morphology. HBE cells were treated with varying doses of CB, fixed, and analyzed via immunocytochemistry. Mitochondria were labelled using a Tom20 antibody conjugate (Alexa488), while microtubules were assessed with phalloidin (Alexa594). Using software developed in MatLab, mitochondria were analyzed for changes in mitochondrial size and localization. Significant changes were identified with regard to an increase in mitochondrial size, and strong trends were observed in an increased localization preference for the perinuclear region. A discussion of the link between elevated ROS levels and mitochondrial behavior will be discussed

DIANA Scheduling Hierarchies for Optimizing Bulk Job Scheduling

The use of meta-schedulers for resource management in large-scale distributed systems often leads to a hierarchy of schedulers. In this paper, we discuss why existing meta-scheduling hierarchies are sometimes not sufficient for Grid systems due to their inability to re-organise jobs already scheduled locally. Such a job re-organisation is required to adapt to evolving loads which are common in heavily used Grid infrastructures. We propose a peer-to-peer scheduling model and evaluate it using case studies and mathematical modelling. We detail the DIANA (Data Intensive and Network Aware) scheduling algorithm and its queue management system for coping with the load distribution and for supporting bulk job scheduling. We demonstrate that such a system is beneficial for dynamic, distributed and self-organizing resource management and can assist in optimizing load or job distribution in complex Grid infrastructures.Comment: 8 pages, 9 figures. Presented at the 2nd IEEE Int Conference on eScience & Grid Computing. Amsterdam Netherlands, December 200

Development of theoretically informed audit and feedback: An exemplar from a complex implementation strategy to improve asthma self-management in UK primary care

RATIONALE: Audit and feedback is an evidence-based implementation strategy, but studies reporting the use of theory to guide design elements are limited. AIMS AND OBJECTIVES: Within the context of a programme of research aiming to improve the implementation of supported asthma self-management in UK primary care (IMPlementing IMProved Asthma self-management as RouTine [IMP2ART]), we aimed to design and develop theoretically-informed audit and feedback that highlighted supported asthma self-management provision and areas for improvement in primary care general practices. METHOD: Aligned with the Medical Research Council (MRC) complex intervention framework, the audit and feedback was developed in three phases: (1) Development: literature and theory exploration, and prototype audit and feedback design; (2) Feasibility: eliciting feedback on the audit and feedback from general practice staff (n = 9); (3) Prepiloting: delivering the audit and feedback within the IMP2ART implementation strategy (incorporating patient and professional resources and an asthma review template) and eliciting clinician feedback (n = 9). RESULTS: Audit and feedback design was guided by and mapped to existing literature suggestions and theory (e.g., Theoretical Domains Framework, Behaviour Change Technique Taxonomy). Feedback on the prototype audit and feedback confirmed feasibility but identified some refinements (a need to highlight supporting self-management and importance of asthma action plans). Prepiloting informed integration with other IMP2ART programme strategies (e.g., patient resources and professional education). CONCLUSION: We conclude that a multistage development process including theory exploration and mapping, contributed to the design and delivery of the audit and feedback. Aligned with the MRC framework, the IMP2ART strategy (incorporating the audit and feedback) is now being tested in a UK-wide cluster randomised controlled trial

A systematic review of interventions addressing limited health literacy to improve asthma self-management

BACKGROUND: Supported asthma self-management improves health outcomes. However, people with limited health literacy, especially in lower-middle-income countries (LMICs), may need tailored interventions to enable them to realise the benefits. We aimed to assess the clinical effectiveness of asthma self-management interventions targeted at people with limited health literacy and to identify strategies associated with effective programmes. METHODS: Following Cochrane methodology, we searched ten databases (January 1990 - June 2018; updated October 2019), without language restriction. We included controlled experimental studies whose interventions targeted health literacy to improve asthma self-management. Selection of papers, extraction of data and quality assessment were done independently by two reviewers. The primary outcomes were clinical (asthma control) and implementation (adoption/adherence to intervention). Analysis was narrative. RESULTS: We screened 4318 titles and abstracts, reviewed 52 full-texts and included five trials. One trial was conducted in a LMIC. Risk of bias was low in one trial and high in the other four studies. Clinical outcomes were reported in two trials, both at high risk of bias: one of which reported a reduction in unscheduled care (number of visits in 6-month (SD); Intervention:0.9 (1.2) vs Control:1.8 (2.4), P = 0.001); the other showed no effect. None reported uptake or adherence to the intervention. Behavioural change strategies typically focused on improving an individual's psychological and physical capacity to enact behaviour (eg, targeting asthma-related knowledge or comprehension). Only two interventions also targeted motivation; none sought to improve opportunity. Less than half of the interventions used specific self-management strategies (eg, written asthma action plan) with tailoring to limited health literacy status. Different approaches (eg, video-based and pictorial action plans) were used to provide education. CONCLUSIONS: The paucity of studies and diversity of the interventions to support people with limited health literacy to self-manage their asthma meant that the impact on health outcomes remains unclear. Given the proportion of the global population who have limited health literacy skills, this is a research priority. PROTOCOL REGISTRATION: PROSPERO CRD 42018118974

Development of theoretically informed audit and feedback: An exemplar from a complex implementation strategy to improve asthma self-management in UK primary care.

RATIONALE: Audit and feedback is an evidence-based implementation strategy, but studies reporting the use of theory to guide design elements are limited. AIMS AND OBJECTIVES: Within the context of a programme of research aiming to improve the implementation of supported asthma self-management in UK primary care (IMPlementing IMProved Asthma self-management as RouTine [IMP2 ART]), we aimed to design and develop theoretically-informed audit and feedback that highlighted supported asthma self-management provision and areas for improvement in primary care general practices. METHOD: Aligned with the Medical Research Council (MRC) complex intervention framework, the audit and feedback was developed in three phases: (1) Development: literature and theory exploration, and prototype audit and feedback design; (2) Feasibility: eliciting feedback on the audit and feedback from general practice staff (n = 9); (3) Prepiloting: delivering the audit and feedback within the IMP2 ART implementation strategy (incorporating patient and professional resources and an asthma review template) and eliciting clinician feedback (n = 9). RESULTS: Audit and feedback design was guided by and mapped to existing literature suggestions and theory (e.g., Theoretical Domains Framework, Behaviour Change Technique Taxonomy). Feedback on the prototype audit and feedback confirmed feasibility but identified some refinements (a need to highlight supporting self-management and importance of asthma action plans). Prepiloting informed integration with other IMP2 ART programme strategies (e.g., patient resources and professional education). CONCLUSION: We conclude that a multistage development process including theory exploration and mapping, contributed to the design and delivery of the audit and feedback. Aligned with the MRC framework, the IMP2 ART strategy (incorporating the audit and feedback) is now being tested in a UK-wide cluster randomised controlled trial

Delivery of supported self-management in remote asthma reviews: A systematic rapid realist review

Background: The COVID-19 pandemic forced health care systems globally to adapt quickly to remote modes of health care delivery, including for routine asthma reviews. A core component of asthma care is supporting self-management, a guideline-recommended intervention that reduces the risk of acute attacks, and improves asthma control and quality of life. Objective: We aimed to explore context and mechanisms for the outcomes of clinical effectiveness, acceptability and safety of supported self-management delivery within remote asthma consultations. Design: The review followed standard methodology for rapid realist reviews. An External Reference Group (ERG) provided expert advice and guidance throughout the study. We systematically searched four electronic databases and, with ERG advice, selected 18 papers that explored self-management delivery during routine asthma reviews. Setting, Participants and Intervention: Health care professional delivery of supported self-management for asthma patients during remote (specifically including telephone and video) consultations. Main Outcome Measures: Data were extracted using Context-Mechanism-Outcome (C-M-O) configurations and synthesised into overarching themes using the PRISMS taxonomy of supported self-management as a framework to structure the findings. Results: The review findings identified how support for self-management delivered remotely was acceptable (often more acceptable than in-person consultations), and was a safe and effective alternative to face-to-face reviews. In addition, remote delivery of supported self-management was associated with; increased patient convenience, improved access to and attendance at remote reviews, and offered continuity of care. Discussion: Remote delivery of supported self-management for asthma was generally found to be clinically effective, acceptable, and safe with the added advantage of increasing accessibility. Remote reviews could provide the core content of an asthma review, including remote completion of asthma action plans. Conclusion: Our findings support the option of remote delivery of routine asthma care for those who have this preference, and offer healthcare professionals guidance on embedding supported self-management into remote asthma reviews. Patient and Public Contribution: Patient and public contribution was provided by a representative of the Asthma UK Centre for Applied Research (AUKCAR) patient and public involvement (PPI) group. The PPI representative reviewed the findings, and feedback and comments were considered. This lead to further interpretations of the data which were included in the final manuscript

Health, Wellbeing, and Social Interaction: An International and Demographic Analysis of Perceived Life Changes and the Positives and Negatives of the COVID-19 Lockdown

Research suggests that people’s experiences of COVID-19 lockdowns have been detrimental to their lives and wellbeing. The current research compared the experiences and perceptions on health, wellbeing and social interaction of 300 UK adults and 450 adults in California. Individuals reported whether aspects of their life had changed for the better, worse, or not at all during lockdown in April 2020, and what the “best” and “worst” things about lockdown were. There were more similarities than differences in the regional comparison of perceptions of changes in specific aspects of ‘health and wellbeing’ and ‘social interaction’. Both regions reported the same number and nature of best and worst things about lockdown. Overarching themes of ‘health, self and wellbeing’, ‘being with others’, and ‘concerns with daily living’ were identified. Although reports of life changes and the positives and negatives of lockdown were similar across different demographic groups, some differences were present by age, sex, relationship, and family-status. Incorporating knowledge of unified and positive experiences of lockdown can be useful in informing future lockdown restrictions and supporting the population when restrictions are lifted

Effectiveness and perceptions of using templates in long-term condition reviews: a systematic synthesis of quantitative and qualitative studies

Background Review templates are commonly used in long-term condition (LTC) consultations to standardise care for patients and promote consistent data recording. However, templates may affect interactions during the review and, potentially, inhibit patient-centred care. Aim To systematically review the literature about the impact that LTC review templates have on process and health outcomes, and the views of health professionals and patients on using review templates in consultations. Design and setting Parallel qualitative and quantitative systematic reviews. Method Following Cochrane methodology, nine databases were searched (1995–2019; updated July 2020) for clinical trials and qualitative studies of LTC templates in healthcare settings. Duplicate selection, risk-of-bias assessment, and data extraction were performed. The quantitative and qualitative analyses were conducted in parallel, and findings synthesised narratively. Results In total, 12 qualitative and 14 quantitative studies were included (two studies reported both qualitative and quantitative data, and were included in both analyses). Review templates were well used, but the only study to assess health outcomes showed no effect. Templates can improve documentation of key measures and act as a reminder tool; however, they can restrict the review process, and risk health professionals’ agendas being prioritised over those of patients. Templates may also limit opportunities to discuss individuals’ concerns about living with their condition and act as a barrier to providing patient-centred care. Conclusion Future research should evaluate health, as well as process, outcomes. The potential benefits of templates in improving documentation should be balanced against concerns that ‘tick boxes’ may override patient agendas, unless templates are designed to promote patient-centred care