Optimising delivery of the Childsmile nursery supervised toothbrushing programme in Scotland

Background. Supervised toothbrushing in nurseries, delivered as a component of Childsmile, Scotland’s national oral health improvement programme for children, is associated with reduced caries experience and cost savings in prevented dental treatments. There is also evidence that it is effective in reducing oral health inequalities, with greater improvements in oral health observed among children living in the most deprived areas. However Childsmile process evaluation data indicate that the nursery supervised toothbrushing programme does not take place as intended in all nursery settings. This highlighted the need to undertake further research to optimise its delivery, to maximise the gains for children’s oral health and contribute to reducing oral health inequalities. Aims: The overarching aim of the research is to optimise delivery of the nursery supervised toothbrushing programme, which is achieved by: further developing its Theory of Change; assessing the fidelity of its implementation compared with the Theory of Change; identifying the barriers and facilitators to its implementation; and identifying implementation strategies to overcome those barriers. It is intended that findings will be fed back into the Childsmile programme to inform ongoing improvement of the nursery supervised toothbrushing programme component. Methods: The research was framed within the paradigm of pragmatism and utilised a mixed-methods approach, informed by a programme theory approach and implementation science methods, making it the first study of its kind to utilise this approach to investigate the implementation of a complex toothbrushing intervention delivered in educational settings. The researcher explicated the programme’s Theory of Change via documentary review, to identify its key components (the inputs, activities and outcomes); and qualitative interviews and focus groups with programme stakeholders, to discuss and agree the Theory of Change, which was depicted in a logic model. Using a mixed methods approach, the researcher undertook national, crosssectional surveys of nurseries, qualitative interviews with programme stakeholders and extracted data from ongoing Childsmile process evaluation, to assess fidelity of implementation and identify barriers and facilitators to delivery. Delivery-in-reality was assessed in comparison with the intended model (per the logic model developed in the previous stage of the research). The researcher used the Consolidated Framework for Implementation Research to categorise the barriers and facilitators identified and mapped these to the Expert Recommendations for Implementing Change compilation of implementation strategies to identify potential methods and techniques to overcome barriers to programme delivery. Results: This novel study identified that optimising the Childsmile nursery supervised toothbrushing programme requires a shared vision to be developed and strengthened among partners involved in its implementation, supported by developing a formal implementation blueprint and further work to increase nursery staff’s buy-in, such as local champions and enhanced training. The fidelity of programme delivery should continue to be monitored and evaluated using the methodology and logic model developed via this research. The inputs, activities and outcomes comprising the Theory of Change of the nursery supervised toothbrushing programme were specified, with consensus on those reached among programme stakeholders. This included stating the primary aim of the programme: 100% of children brush their teeth in nursery, every day they attend. However, national survey results showed that this target was not met, with 92% of eligible children brushing in nurseries on the day of the survey and variation in percentages of children brushing across geographical health boards. Nurseries with 100% toothbrushing rates were more likely to have fewer children attending, only have a single age group attending and were situated in certain geographical health board areas and not others. Using a mixed methods approach highlighted inconsistencies between these quantitative data on nurseries’ participation and qualitative findings on stakeholders’ perceptions about nurseries’ participation. There were variations between health boards in the extent to which delivery-in-reality matched what was intended. This included the content and frequency of training provided to nursery staff to support their delivery of the programme, with no standardised training package available nationally. Relationships between Childsmile teams and local authorities’ education departments were identified as important although these required careful management and communication. Barriers and facilitators influencing programme implementation before and during the Covid19 pandemic were identified and the Consolidated Framework for Implementation Research provided good coverage of these (encompassing all five domains and 14 out of 26 constructs associated with intervention implementation). Relevant constructs included: ‘Complexity’, in relation to fitting toothbrushing in to nursery routines and perceptions about it being too time-consuming; ‘Patient Needs and Resources’, in terms of children’s ability to perform the required actions as well as their reluctance to participate in toothbrushing instead of other available activities; and ‘External Policies and Incentives’, which related to the interpretation of early years policies which conflicted with directing children to participate in activities, including toothbrushing. An overarching theme related to the prioritisation of the nursery supervised toothbrushing programme by nursery staff, including the extent to which other activities were given precedence over it; and nursery staff’s willingness to accommodate toothbrushing flexibly within nursery schedules. The Covid-19 pandemic disrupted delivery of the programme due to nursery closures in 2020 and 2021, as well as creating additional pressures for nursery staff once establishments reopened. This affected the extent to which they engaged with efforts to restart the toothbrushing programme. Conclusions: This research has explicated the Theory of Change for Childsmile’s nursery supervised toothbrushing programme, from the perspective of programme stakeholders. There is scope for further specification of core, ‘essential’ programme components and adaptable, peripheral components, to identify an acceptable level of delivery which will allow progress towards outcomes. There are also opportunities to work with stakeholders from other organisations, aside from Childsmile, to identify changes to the Theory of Change to enhance its fit with their needs and priorities. In assessing the fidelity of programme implementation, it was found that aspects were delivered as intended; however, most logic model activities had components that were not being delivered with fidelity, including that less than 100% of children brushed their teeth every day they attended nursery. It was identified that the nursery context in which the programme is delivered was complex and fluctuating, with competing demands on nursery staff’s time. This indicated a need to accept that the programme has to fit within overall nursery provision, to ensure it is given enough priority. This requires identifying implementation strategies to find ways to help it fit alongside other priorities, including strategies to enhance engagement among nursery staff while taking their perspectives into account. A number of recommendations are made to support and optimise programme delivery going forward. These include supplementing the programme’s ongoing work in fostering relationships with partners with a focused communications campaign, targeted at stakeholders in individual nurseries and local authority education departments, which demonstrates how the programme fits within the wider nursery curriculum and its contribution to children’s health and wellbeing alongside information (tailored to stakeholders’ roles) that clarifies what is involved in programme delivery. It is also recommended that a knowledge exchange and support network should be established among nurseries, led by champions (invited to undertake this role among nursery staff with an interest in oral health working in nurseries identified to deliver the programme well) who support and mentor their peers to overcome challenges to delivering the toothbrushing programme. This could include enhanced training, tailored to individual nurseries’ needs, to provide practical solutions to overcome challenges encountered. To encourage participation among local authorities’ education departments and individual establishments’ head teachers and managers, it is recommended that further, supportive dialogue takes place between the Childsmile programme, the Scottish Government and local authority education departments

Patients' and partners' health-related quality of life before and 4 months after coronary artery bypass grafting surgery

Background: Patients having coronary artery bypass grafting (CABG) often depend on their partners for assistance before and after surgery. Whilst patients' physical and mental health usually improves after surgery little is known about the partners' health-related quality of life (HRQoL) in CABG. If the partners' physical and emotional health is poor this can influence their caregiving role and ability to support the patient. This study aimed: to increase understanding of patients' and partners' HRQoL before and after CABG; to explore whether patients' and partners' pre-operative socio-demographics and HRQoL predict their own, and also partners' HRQoL 4 months after CABG. Methods: This prospective study recruited 84 dyads (patients 84% males, aged 64.5 years; partners 94% females, aged 61.05 years). Patients' and partners' perceived health status was assessed using the Short-Form 12 Health Survey. Patients' physical limitation, angina symptoms and treatment satisfaction were assessed using the Seattle Angina Questionnaire. Partners' emotional, physical and social functioning was assessed using the Quality of Life of Cardiac Spouses Questionnaire. Data were analysed using hierarchical multiple (logistic) regressions, repeated measures analysis of variance, paired t test and Chi square. Results: Patients most likely to have poorer physical health post-operatively were associated with partners who had poorer pre-operative physical health. Partners most likely to have poorer emotional, physical and social functioning post-operatively were associated with patients who had poorer pre-operative mental health. Patients" and partners' poorer post-operative HRQoL was also explained by their poorer pre-operative HRQoL. Conclusion: The partners' involvement should be considered as part of patients' pre-operative assessment. Special attention needs be paid to patients' pre-operative mental health since it is likely to impact on their post-operative mental health and the partner's emotional, physical and social functioning

Graphene-hexagonal boron nitride resonant tunneling diodes as high-frequency oscillators

We assess the potential of two-terminal graphene-hexagonal boron nitride-graphene resonant tunneling diodes as high-frequency oscillators, using self-consistent quantum transport and electrostatic simulations to determine the time-dependent response of the diodes in a resonant circuit. We quantify how the frequency and power of the current oscillations depend on the diode and circuit parameters including the doping of the graphene electrodes, device geometry, alignment of the graphene lattices, and the circuit impedances. Our results indicate that current oscillations with frequencies of up to several hundred GHz should be achievable

Can programme theory be used as a 'translational tool’ to optimise health service delivery in a national early years’ initiative in Scotland: a case study

Background Theory-based evaluation (TBE) approaches are heralded as supporting formative evaluation by facilitating increased use of evaluative findings to guide programme improvement. It is essential that learning from programme implementation is better used to improve delivery and to inform other initiatives, if interventions are to be as effective as they have the potential to be. Nonetheless, few studies describe formative feedback methods, or report direct instrumental use of findings resulting from TBE. This paper uses the case of Scotland’s, National Health Service, early years’, oral health improvement initiative (Childsmile) to describe the use of TBE as a framework for providing feedback on delivery to programme staff and to assess its impact on programmatic action.<p></p> Methods In-depth, semi-structured interviews and focus groups with key stakeholders explored perceived deviations between the Childsmile programme 'as delivered’ and its Programme Theory (PT). The data was thematically analysed using constant comparative methods. Findings were shared with key programme stakeholders and discussions around likely impact and necessary actions were facilitated by the authors. Documentary review and ongoing observations of programme meetings were undertaken to assess the extent to which learning was acted upon.<p></p> Results On the whole, the activities documented in Childsmile’s PT were implemented as intended. This paper purposefully focuses on those activities where variation in delivery was evident. Differences resulted from the stage of roll-out reached and the flexibility given to individual NHS boards to tailor local implementation. Some adaptations were thought to have diverged from the central features of Childsmile’s PT, to the extent that there was a risk to achieving outcomes. The methods employed prompted national service improvement action, and proposals for local action by individual NHS boards to address this.<p></p> Conclusions The TBE approach provided a platform, to direct attention to areas of risk within a national health initiative, and to agree which intervention components were 'core’ to its hypothesised success. The study demonstrates that PT can be used as a 'translational tool’ to facilitate instrumental use of evaluative findings to optimise implementation within a complex health improvement programme.<p></p&gt

The Vaginal Microbiome: Disease, Genetics and the Environment

The vagina is an interactive interface between the host and the environment. Its surface is covered by a protective epithelium colonized by bacteria and other microorganisms. The ectocervix is nonsterile, whereas the endocervix and the upper genital tract are assumed to be sterile in healthy women. Therefore, the cervix serves a pivotal role as a gatekeeper to protect the upper genital tract from microbial invasion and subsequent reproductive pathology. Microorganisms that cross this barrier can cause preterm labor, pelvic inflammatory disease, and other gynecologic and reproductive disorders. Homeostasis of the microbiome in the vagina and ectocervix plays a paramount role in reproductive health. Depending on its composition, the microbiome may protect the vagina from infectious or non-infectious diseases, or it may enhance its susceptibility to them. Because of the nature of this organ, and the fact that it is continuously colonized by bacteria from birth to death, it is virtually certain that this rich environment evolved in concert with its microbial flora. Specific interactions dictated by the genetics of both the host and microbes are likely responsible for maintaining both the environment and the microbiome. However, the genetic basis of these interactions in both the host and the bacterial colonizers is currently unknown. _Lactobacillus_ species are associated with vaginal health, but the role of these species in the maintenance of health is not yet well defined. Similarly, other species, including those representing minor components of the overall flora, undoubtedly influence the ability of potential pathogens to thrive and cause disease. Gross alterations in the vaginal microbiome are frequently observed in women with bacterial vaginosis, but the exact etiology of this disorder is still unknown. There are also implications for vaginal flora in non-infectious conditions such as pregnancy, pre-term labor and birth, and possibly fertility and other aspects of women’s health. Conversely, the role of environmental factors in the maintenance of a healthy vaginal microbiome is largely unknown. To explore these issues, we have proposed to address the following questions:

*1.	Do the genes of the host contribute to the composition of the vaginal microbiome?* We hypothesize that genes of both host and bacteria have important impacts on the vaginal microbiome. We are addressing this question by examining the vaginal microbiomes of mono- and dizygotic twin pairs selected from the over 170,000 twin pairs in the Mid-Atlantic Twin Registry (MATR). Subsequent studies, beyond the scope of the current project, may investigate which host genes impact the microbial flora and how they do so.
*2.	What changes in the microbiome are associated with common non-infectious pathological states of the host?* We hypothesize that altered physiological (e.g., pregnancy) and pathologic (e.g., immune suppression) conditions, or environmental exposures (e.g., antibiotics) predictably alter the vaginal microbiome. Conversely, certain vaginal microbiome characteristics are thought to contribute to a woman’s risk for outcomes such as preterm delivery. We are addressing this question by recruiting study participants from the ~40,000 annual clinical visits to women’s clinics of the VCU Health System.
*3.	What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions?* We hypothesize that susceptibility to infectious disease (e.g. HPV, _Chlamydia_ infection, vaginitis, vaginosis, etc.) is impacted by the vaginal microbiome. In turn, these infectious conditions clearly can affect the ability of other bacteria to colonize and cause pathology. Again, we are exploring these issues by recruiting participants from visitors to women’s clinics in the VCU Health System.

Three kinds of sequence data are generated in this project: i) rDNA sequences from vaginal microbes; ii) whole metagenome shotgun sequences from vaginal samples; and iii) whole genome shotgun sequences of bacterial clones selected from vaginal samples. The study includes samples from three vaginal sites: mid-vaginal, cervical, and introital. The data sets also include buccal and perianal samples from all twin participants. Samples from these additional sites are used to test the hypothesis of a per continuum spread of bacteria in relation to vaginal health. An extended set of clinical metadata associated with these sequences are deposited with dbGAP. We have currently collected over 4,400 samples from ~100 twins and over 450 clinical participants. We have analyzed and deposited data for 480 rDNA samples, eight whole metagenome shotgun samples, and over 50 complete bacterial genomes. These data are available to accredited investigators according to NIH and Human Microbiome Project (HMP) guidelines. The bacterial clones are deposited in the Biodefense and Emerging Infections Research Resources Repository ("http://www.beiresources.org/":http://www.beiresources.org/). 

In addition to the extensive sequence data obtained in this study, we are collecting metadata associated with each of the study participants. Thus, participants are asked to complete an extensive health history questionnaire at the time samples are collected. Selected clinical data associated with the visit are also obtained, and relevant information is collected from the medical records when available. This data is maintained securely in a HIPAA-compliant data system as required by VCU’s Institutional Review Board (IRB). The preponderance of these data (i.e., that judged appropriate by NIH staff and VCU’s IRB are deposited at dbGAP ("http://www.ncbi.nlm.nih.gov/gap":http://www.ncbi.nlm.nih.gov/gap). Selected fields of this data have been identified by NIH staff as ‘too sensitive’ and are not available in dbGAP. Individuals requiring access to these data fields are asked to contact the PI of this project or NIH Program Staff. 
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Protection Afforded by Fluoroquinolones in Animal Models of Respiratory Infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis

Successful treatment of inhalation anthrax, pneumonic plague and tularemia can be achieved with fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. Bacillus anthracis Ames, Yersinia pestis CO92, and Francisella tularensis SCHU S4 have equivalent susceptibility in vitro to ciprofloxacin and levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited information is available regarding in vivo susceptibility of these infectious agents to the fluoroquinolone antibiotics in small animal models. Mice, guinea pig, and rabbit models have been developed to evaluate the protective efficacy of antibiotic therapy against these life-threatening infections. Our results indicated that doses of ciprofloxacin and levofloxacin required to protect mice against inhalation anthrax were approximately 18-fold higher than the doses of levofloxacin required to protect against pneumonic plague and tularemia. Further, the critical period following aerosol exposure of mice to either B. anthracis spores or Y. pestis was 24 h, while mice challenged with F. tularensis could be effectively protected when treatment was delayed for as long as 72 h postchallenge. In addition, it was apparent that prolonged antibiotic treatment was important in the effective treatment of inhalation anthrax in mice, but short-term treatment of mice with pneumonic plague or tularemia infections were usually successful. These results provide effective antibiotic dosages in mice, guinea pigs, and rabbits and lay the foundation for the development and evaluation of combinational treatment modalities

Human Salmonella and Concurrent Decreased Susceptibility to Quinolones and Extended-Spectrum Cephalosporins

For complicated infections, decreased susceptibility could compromise treatment with drugs from either antimicrobial class

LongSAGE profiling of nine human embryonic stem cell lines

Analysis of a 2.6 million longSAGE sequence tag resource generated from nine human embryonic stem cell lines reveals an enrichment of RNA binding proteins and novel ES-specific transcripts

Meta-Analysis of Differentiating Mouse Embryonic Stem Cell Gene Expression Kinetics Reveals Early Change of a Small Gene Set

Stem cell differentiation involves critical changes in gene expression. Identification of these should provide endpoints useful for optimizing stem cell propagation as well as potential clues about mechanisms governing stem cell maintenance. Here we describe the results of a new meta-analysis methodology applied to multiple gene expression datasets from three mouse embryonic stem cell (ESC) lines obtained at specific time points during the course of their differentiation into various lineages. We developed methods to identify genes with expression changes that correlated with the altered frequency of functionally defined, undifferentiated ESC in culture. In each dataset, we computed a novel statistical confidence measure for every gene which captured the certainty that a particular gene exhibited an expression pattern of interest within that dataset. This permitted a joint analysis of the datasets, despite the different experimental designs. Using a ranking scheme that favored genes exhibiting patterns of interest, we focused on the top 88 genes whose expression was consistently changed when ESC were induced to differentiate. Seven of these (103728_at, 8430410A17Rik, Klf2, Nr0b1, Sox2, Tcl1, and Zfp42) showed a rapid decrease in expression concurrent with a decrease in frequency of undifferentiated cells and remained predictive when evaluated in additional maintenance and differentiating protocols. Through a novel meta-analysis, this study identifies a small set of genes whose expression is useful for identifying changes in stem cell frequencies in cultures of mouse ESC. The methods and findings have broader applicability to understanding the regulation of self-renewal of other stem cell types