89 research outputs found

    Developing and evaluating the implementation of a complex intervention: using mixed methods to inform the design of a randomised controlled trial of an oral healthcare intervention after stroke

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    <p>Abstract</p> <p>Background</p> <p>Many interventions delivered within the stroke rehabilitation setting could be considered complex, though some are more complex than others. The degree of complexity might be based on the number of and interactions between levels, components and actions targeted within the intervention. The number of (and variation within) participant groups and the contexts in which it is delivered might also reflect the extent of complexity. Similarly, designing the evaluation of a complex intervention can be challenging. Considerations include the necessity for intervention standardisation, the multiplicity of outcome measures employed to capture the impact of a multifaceted intervention and the delivery of the intervention across different clinical settings operating within varying healthcare contexts. Our aim was to develop and evaluate the implementation of a complex, multidimensional oral health care (OHC) intervention for people in stroke rehabilitation settings which would inform the development of a randomised controlled trial.</p> <p>Methods</p> <p>After reviewing the evidence for the provision of OHC following stroke, multi-disciplinary experts informed the development of our intervention. Using both quantitative and qualitative methods we evaluated the implementation of the complex OHC intervention across patients, staff and service levels of care. We also adopted a pragmatic approach to patient recruitment, the completion of assessment tools and delivery of OHC, alongside an attention to the context in which it was delivered.</p> <p>Results</p> <p>We demonstrated the feasibility of implementing a complex OHC intervention across three levels of care. The complementary nature of the mixed methods approach to data gathering provided a complete picture of the implementation of the intervention and a detailed understanding of the variations within and interactions between the components of the intervention. Information on the feasibility of the outcome measures used to capture impact across a range of components was also collected, though some process orientated uncertainties including eligibility and recruitment rates remain to be further explored within a Phase II exploratory trial.</p> <p>Conclusions</p> <p>Complex interventions can be captured and described in a manner which facilitates evaluation in the form of exploratory and subsequently definitive clinical trials. If effective, the evidence captured relating to the intervention context will facilitate translation into clinical practice.</p

    Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

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    Ying Yang 1 (YY1) is a multifunctional Polycomb Group (PcG) transcription factor that binds to multiple enhancer binding sites in the immunoglobulin (Ig) loci and plays vital roles in early B cell development. PcG proteins have important functions in hematopoietic stem cell renewal and YY1 is the only mammalian PcG protein with DNA binding specificity. Conditional knock-out of YY1 in the mouse B cell lineage results in arrest at the pro-B cell stage, and dosage effects have been observed at various YY1 expression levels. To investigate the impact of elevated YY1 expression on hematopoetic development, we utilized a mouse in vivo bone marrow reconstitution system. We found that mouse bone marrow cells expressing elevated levels of YY1 exhibited a selective disadvantage as they progressed from hematopoietic stem/progenitor cells to pro-B, pre-B, immature B and re-circulating B cell stages, but no disadvantage of YY1 over-expression was observed in myeloid lineage cells. Furthermore, mouse bone marrow cells expressing elevated levels of YY1 displayed enrichment for cells with surface markers characteristic of long-term hematopoietic stem cells (HSC). YY1 expression induced apoptosis in mouse B cell lines in vitro, and resulted in down-regulated expression of anti-apoptotic genes Bcl-xl and NFκB2, while no impact was observed in a mouse myeloid line. B cell apoptosis and LT-HSC enrichment induced by YY1 suggest that novel strategies to induce YY1 expression could have beneficial effects in the treatment of B lineage malignancies while preserving normal HSCs

    Systemic 7-methylxanthine in retarding axial eye growth and myopia progression: a 36-month pilot study

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    The adenosine antagonist 7-methylxanthine (7-mx) works against myopia in animal models. In a clinical trial, 68 myopic children (mean age 11.3 years) received either placebo or 7-mx tablets for 12 months. All participants subsequently received 7-mx for another 12 months, after which treatment was stopped. Axial length was measured with Zeiss IOL-Master and cycloplegic refraction with Nikon Retinomax at −6, 0, 12, 24, and 36 months. Axial growth was reduced among children treated with 7-mx for 24 months compared with those only treated for the last 12 months. Myopia progression and axial eye growth slowed down in periods with 7-mx treatment, but when the treatment was stopped, both myopia progression and axial eye growth continued with invariable speed. The results indicate that 7-mx reduces eye elongation and myopia progression in childhood myopia. The treatment is safe and without side effects and may be continued until 18–20 years of age when myopia progression normally stops

    Doing the plastic fantastic: ‘artificial’ adventure and older adult climbers

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    The aim of this article is to determine the perceptions and experiences of climbing at artificial climbing walls (ACWs) as undertaken by a cohort of ‘young-old’ people (approximately 65–75 years). The engagement of older people in outdoor activities and adventure is an evolving topic; however, as part of this development, little has been written on the use of ACWs. Methodologically, the research employed in-depth semi-structured focus groups and interviews with a purposive convenience sample of six recreational climbers, subsequently expanded to ten through snowball technique. Both sexes were equally represented. Manual thematic analysis identified two key motifs: ACWs and the notion of adventure, and ACWs and the potential for learning. The findings point at what constitutes ‘real’ adventure for this group of older adults; the shifting nature of ‘old age’; the significance of self-awareness; and the role of reflexivity and physical activity in the construction of a ‘successful’ old age

    A review of the benefits and drawbacks to virtual field guides in today’s Geoscience higher education environment

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    Virtual Field Guides are a way for educators to tackle the growing issue of funding pressures in areas of higher education, such as geography. Virtual Field Guides are however underutilised and can offer students a different way of learning. Virtual Field Guides have many benefits to students, such as being more inclusive, building student skills and confidence in a controlled environment pre fieldtrip and can increase engagement in the topic studied. There are also benefits to the educator, such as reduced cost, more efficient students on fieldwork tasks and the ability to tailor and update their field guides to suit their needs. However there are drawbacks in the challenge of creation and their outcome as educational standalone tools. This paper reviews the literature around the benefits and draw backs to the creation and incorporation of virtual field guides in geoscience education. © 2017, The Author(s)

    Drug discovery: Insights from the invertebrate Caenorhabditis elegans

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    Therapeutic drug development is a long, expensive, and complex process that usually takes 12–15 years. In the early phases of drug discovery, in particular, there is a growing need for animal models that ensure the reduction in both cost and time. Caenorhabditis elegans has been traditionally used to address fundamental aspects of key biological processes, such as apoptosis, aging, and gene expression regulation. During the last decade, with the advent of large-scale platforms for screenings, this invertebrate has also emerged as an essential tool in the pharmaceutical research industry to identify novel drugs and drug targets. In this review, we discuss the reasons why C. elegans has been positioned as an outstanding cost-effective option for drug discovery, highlighting both the advantages and drawbacks of this model. Particular attention is paid to the suitability of this nematode in large-scale genetic and pharmacological screenings. High-throughput screenings in C. elegans have indeed contributed to the breakthrough of a wide variety of candidate compounds involved in extensive fields including neurodegeneration, pathogen infections and metabolic disorders. The versatility of this nematode, which enables its instrumentation as a model of human diseases, is another attribute also herein underscored. As illustrative examples, we discuss the utility of C. elegans models of both human neurodegenerative diseases and parasitic nematodes in the drug discovery industry. Summing up, this review aims to demonstrate the impact of C. elegans models on the drug discovery pipeline.Fil: Giunti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Andersen, Natalia Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Rayes, Diego Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: de Rosa, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentin

    SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

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    Background: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods: We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results: We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions: As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals. © 2022, The Author(s)
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