BackgroundA multitude of theories, models and frameworks relating to implementing evidence-based practice in health care exist, which can be overwhelming for clinicians and clinical researchers new to the field of implementation science. Clinicians often bear responsibility for implementation, but may be unfamiliar with theoretical approaches designed to inform or understand implementation.Main textIn this article, a multidisciplinary group of clinicians and health service researchers present a pragmatic guide to help clinicians and clinical researchers understand what implementation theories, models and frameworks are; how a theoretical approach to implementation might be used; and some prompts to consider when selecting a theoretical approach for an implementation project. Ten commonly used and highly cited theoretical approaches are presented, none of which have been utilised to their full potential in the literature to date. Specifically, theoretical approaches tend to be applied retrospectively to evaluate or interpret findings from a completed implementation project, rather than being used to plan and design theory-informed implementation strategies which would intuitively have a greater likelihood of success. We emphasise that there is no right or wrong way of selecting a theoretical approach, but encourage clinicians to carefully consider the project’s purpose, scope and available data and resources to allow them to select an approach that is most likely to “value-add” to the implementation project.ConclusionBy assisting clinicians and clinical researchers to become confident in selecting and applying theoretical approaches to implementation, we anticipate an increase in theory-informed implementation projects. This then will contribute to more nuanced advice on how to address evidence-practice gaps and ultimately to contribute to better health outcomes.Electronic supplementary materialThe online version of this article (10.1186/s12913-018-3671-z) contains supplementary material, which is available to authorized users.
SUMMARYThe biosynthesis of the tocotrienol and tocopherol forms of vitamin E is initiated by prenylation of homogentisate. Geranylgeranyl diphosphate (GGDP) is the prenyl donor for tocotrienol synthesis, whereas phytyl diphosphate (PDP) is the prenyl donor for tocopherol synthesis. We have previously shown that tocotrienol synthesis is initiated in monocot seeds by homogentisate geranylgeranyl transferase (HGGT). This enzyme is related to homogentisate phytyltransferase (HPT), which catalyzes the prenylation step in tocopherol synthesis. Here we show that monocot HGGT is localized in the plastid and expressed primarily in seed endosperm. Despite the close structural relationship of monocot HGGT and HPT, these enzymes were found to have distinct substrate specificities. Barley (Hordeum vulgare cv. Morex) HGGT expressed in insect cells was six times more active with GGDP than with PDP, whereas the Arabidopsis HPT was nine times more active with PDP than with GGDP. However, only small differences were detected in the apparent K m values of barley HGGT for GGDP and PDP. Consistent with its in vitro substrate properties, barley HGGT generated a mixture of tocotrienols and tocopherols when expressed in the vitamin E-null vte2-1 mutant lacking a functional HPT. Relative levels of tocotrienols and tocopherols produced in vte2-1 differed between organs and growth stages, reflective of the composition of plastidic pools of GGDP and PDP. In addition, HGGT was able to functionally substitute for HPT to rescue vte2-1-associated phenotypes, including reduced seed viability and increased fatty acid oxidation of seed lipids. Overall, we show that monocot HGGT is biochemically distinct from HPT, but can replace HPT in important vitamin E-related physiological processes.
Naturally occurring vitamin E, comprised of four forms each of tocopherols and tocotrienols, are synthesized solely by photosynthetic organisms and function primarily as antioxidants. These different forms vary in their biological availability and in their physiological and chemical activities. Tocopherols and tocotrienols play important roles in the oxidative stability of vegetable oils and in the nutritional quality of crop plants for human and livestock diets. The isolation of genes for nearly all the steps in tocopherol and tocotrienol biosynthesis has facilitated efforts to alter metabolic flux through these pathways in plant cells. Herein we review the recent work done in the field, focusing on branch points and metabolic engineering to enhance and alter vitamin E content and composition in oilseed crops.
Recently, there has been a growing interest in what is positioned as a new form of masculinity arising from the increase in fathers as primary caregivers. This new form is referred to as a “caring masculinity” and is theorised as a radical shift away from traditional or hegemonic forms of masculinity. This paper critically examines the fathering literature, focusing specifically on how primary caregiving fathers navigate social norms with regard to masculinity. The paper concludes that there is a complex interplay between expectations of a traditional, provider father and a new and involved father. It is argued that ideas surrounding a caring masculinity are better understood as a broadening of hegemonic masculinity, rather than an entirely new or distinct form.
SUMMARYVitamin E tocotrienol synthesis in monocots requires homogentisate geranylgeranyl transferase (HGGT), which catalyzes the condensation of homogentisate and the unsaturated C20 isoprenoid geranylgeranyl diphosphate (GGDP). By contrast, vitamin E tocopherol synthesis is mediated by homogentisate phytyltransferase (HPT), which condenses homogentisate and the saturated C20 isoprenoid phytyl diphosphate (PDP). An HGGT-independent pathway for tocotrienol synthesis has also been shown to occur by de-regulation of homogentisate synthesis. In this paper, the basis for this pathway and its impact on vitamin E production when combined with HGGT are explored. An Arabidopsis line was initially developed that accumulates tocotrienols and homogentisate by co-expression of Arabidopsis hydroxyphenylpyruvate dioxygenase (HPPD) and Escherichia coli bi-functional chorismate mutase/prephenate dehydrogenase (TyrA). When crossed into the vte2-1 HPT null mutant, tocotrienol production was lost, indicating that HPT catalyzes tocotrienol synthesis in HPPD/TyrA-expressing plants by atypical use of GGDP as a substrate. Consistent with this, recombinant Arabidopsis HPT preferentially catalyzed in vitro production of the tocotrienol precursor geranylgeranyl benzoquinol only when presented with high molar ratios of GGDP:PDP. In addition, tocotrienol levels were highest in early growth stages in HPPD/TyrA lines, but decreased strongly relative to tocopherols during later growth stages when PDP is known to accumulate. Collectively, these results indicate that HPPD/TyrA-induced tocotrienol production requires HPT and occurs upon enrichment of GGDP relative to PDP in prenyl diphosphate pools. Finally, combined expression of HPPD/TyrA and HGGT in Arabidopsis leaves and seeds resulted in large additive increases in vitamin E production, indicating that homogentisate concentrations limit HGGT-catalyzed tocotrienol synthesis.
Background: The Promoting Action on Research Implementation in Health Services (PARIHS) framework was developed two decades ago and conceptualizes successful implementation (SI) as a function (f) of the evidence (E) nature and type, context (C) quality, and the facilitation (F), [SI = f (E,C,F)]. Despite a growing number of citations of theoretical frameworks including PARIHS, details of how theoretical frameworks are used remains largely unknown. This review aimed to enhance the understanding of the breadth and depth of the use of the PARIHS framework. Methods: This citation analysis commenced from four core articles representing the key stages of the framework's development. The citation search was performed in Web of Science and Scopus. After exclusion, we undertook an initial assessment aimed to identify articles using PARIHS and not only referencing any of the core articles. To assess this, all articles were read in full. Further data extraction included capturing information about where (country/ countries and setting/s) PARIHS had been used, as well as categorizing how the framework was applied. Also, strengths and weaknesses, as well as efforts to validate the framework, were explored in detail. Results: The citation search yielded 1613 articles. After applying exclusion criteria, 1475 articles were read in full, and the initial assessment yielded a total of 367 articles reported to have used the PARIHS framework. These articles were included for data extraction. The framework had been used in a variety of settings and in both high-, middle-, and low-income countries. With regard to types of use, 32% used PARIHS in planning and delivering an intervention, 50% in data analysis, 55% in the evaluation of study findings, and/or 37% in any other way. Further analysis showed that its actual application was frequently partial and generally not well elaborated. Conclusions: In line with previous citation analysis of the use of theoretical frameworks in implementation science, we also found a rather superficial description of the use of PARIHS. Thus, we propose the development and adoption of reporting guidelines on how framework(s) are used in implementation studies, with the expectation that this will enhance the maturity of implementation science.
Background: The integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework is an implementation framework that has been developed and refined over the last 20 years. Its underlying philosophy is that implementing research into healthcare practice is complex, unpredictable and nonlinear which therefore requires a flexible and responsive approach to implementation. Facilitation is recognized as the central ingredient of this approach, and i-PARIHS now provides a Facilitation Guide with associated tools. This multiple case study of four implementation projects explored how the i-PARIHS framework has been practically operationalized by diverse implementation project teams. Methods: A co-design approach was used to elicit the experiences of four implementation project teams who used the i-PARIHS framework to guide their implementation approach. We conducted the established co-design steps of (i) setting up for success, (ii) gathering the experience, and (iii) understanding the experience. In particular we explored teams' approaches to setting up their projects; why and how they used the i-PARIHS framework and what they learnt from the experience. Results: We found both commonalities and differences in the use of i-PARIHS across the four implementation projects: (i) all the projects used the Facilitation Checklist that accompanies i-PARIHS as a starting point, (ii) the projects differed in how facilitation was carried out, (iii) existing tools were adapted for distinct phases: preimplementation, during implementation, and post-implementation stages; and (iv) project-specific tools were often developed for monitoring implementation activities and fidelity. Conclusions: We have provided a detailed overview of how current users of i-PARIHS are operationalising the framework, which existing tools they are using or adapting to use, and where they have needed to develop new tools to best utilise the framework. Importantly, this study highlights the value of existing tools from the published i-PARIHS Facilitation Guide and provides a starting point to further refine and add to these tools within a future Mobilising Implementation of i-PARIHS (or "Mi-PARIHS") suite of resources. Specifically, Mi-PARIHS might include more explicit guidance and/or tools for developing a structured implementation plan and monitoring fidelity to the implementation plan, including recording how strategies are tailored to an evolving context.
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