Optimising the conceptualisation of context; comment on "Stakeholder Perspectives of Attributes and Features of Context Relevant to Knowledge Translation in Health Settings: A Multi-Country Analysis"

Context matters. Therefore, efforts to develop greater conceptual clarity are important for science and practice. In this commentary, we outline some key issues that were prompted by Squire’s et al.’s contribution. Specifically, we reinforce context as an interactive concept and therefore something that is hard to ‘pin down’, the problematic nature of conceptualising context in implementation and de-implementation, and a requirement for the development of culturally sensitive understandings. Finally, we suggest it is vital that continued investment into providing a more comprehensive list of determinants needs to be accompanied by an equal effort in developing practical methods and tools to support use and application

What can management theories offer evidence-based practice? A comparative analysis of measurement tools for organisational context

Background: Given the current emphasis on networks as vehicles for innovation and change in health service delivery, the ability to conceptualise and measure organisational enablers for the social construction of knowledge merits attention. This study aimed to develop a composite tool to measure the organisational context for evidence-based practice (EBP) in healthcare. Methods: A structured search of the major healthcare and management databases for measurement tools from four domains: research utilisation (RU), research activity (RA), knowledge management (KM), and organisational learning (OL). Included studies were reports of the development or use of measurement tools that included organisational factors. Tools were appraised for face and content validity, plus development and testing methods. Measurement tool items were extracted, merged across the four domains, and categorised within a constructed framework describing the absorptive and receptive capacities of organisations. Results: Thirty measurement tools were identified and appraised. Eighteen tools from the four domains were selected for item extraction and analysis. The constructed framework consists of seven categories relating to three core organisational attributes of vision, leadership, and a learning culture, and four stages of knowledge need, acquisition of new knowledge, knowledge sharing, and knowledge use. Measurement tools from RA or RU domains had more items relating to the categories of leadership, and acquisition of new knowledge; while tools from KM or learning organisation domains had more items relating to vision, learning culture, knowledge need, and knowledge sharing. There was equal emphasis on knowledge use in the different domains. Conclusion: If the translation of evidence into knowledge is viewed as socially mediated, tools to measure the organisational context of EBP in healthcare could be enhanced by consideration of related concepts from the organisational and management sciences. Comparison of measurement tools across domains suggests that there is scope within EBP for supplementing the current emphasis on human and technical resources to support information uptake and use by individuals. Consideration of measurement tools from the fields of KM and OL shows more content related to social mechanisms to facilitate knowledge recognition, translation, and transfer between individuals and groups

HST Paschen alpha and 1.9 micron imaging of Sgr A West

We present HST/NICMOS images at 0.2" resolution of the HI Paschen Alpha (PaA) emission line in a 70" x 90" region of the Galactic center centered on the non-thermal radio source Sgr A*. The majority of the emission arises from ionized gas in the mini-spiral in the central parsec. PaA emission is also seen from 26 stellar sources, presumably early-type stars with mass-loss winds. The new data reveal significant small-scale structure (<1"~0.04pc) in the ionized gas of the mini-spiral; low surface brightness emission features are also seen for the first time. Extinction, estimated from the ratio of observed PaA emission to 6-cm continuum emission, varies from 20 to 50 mag with a median Av=31.1 mag, in excellent agreement with earlier estimates for the stellar sources and indepedent measurements derived using H92alpha recombination line data. Large increases in extinction are seen along the periphery of the ionized gas, suggesting that the ionized gas is partially extincted by dust in the molecular clouds at the outside of the ionized regions. The small-scale, filamentary structures in the ionized gas have a free thermal expansion time of only ~ 3000 yrs; either magnetic fields or mass-loss winds from the hot emission line stars may contain the ionized filaments. For both the ionized gas and the stellar continuum, the centroids of the emission remain within ~+/- 1" from a radius of 2" out to 40", providing further evidence that Sgr A* is indeed at or extremely close to the dynamical center of the Galactic nucleus stellar distribution. The 1.9 micron surface brightness increases inwards to 0.9" and then decreases or levels off closer to Sgr A*, possibly indicating the core radius of the central stellar distribution or depletion of the late-type stars by stellar collisions near the central black hole.Comment: 43 pages, 15 figures, 2 tables; Accepted to ApJ (9/1/03 issue

Resource based view of the firm as a theoretical lens on the organisational consequences of quality improvement

Evaluating the investment that healthcare organisations make in quality improvement requires knowledge of impact at multiple levels, including patient care, workforce and other organisational resources. The degree to which these resources help organisations to survive and thrive in the challenging contexts in which healthcare is designed and delivered is unknown. Investigating this question from the perspective of the Resource Based View (RBV) of the Firm may provide insights, although is not without challenge

Complete replication of hepatitis C virus in cell culture.

Many aspects of the hepatitis C virus (HCV) life cycle have not been reproduced in cell culture, which has slowed research progress on this important human pathogen. Here, we describe a full-length HCV genome that replicates and produces virus particles that are infectious in cell culture (HCVcc). Replication of HCVcc was robust, producing nearly 10(5) infectious units per milliliter within 48 hours. Virus particles were filterable and neutralized with a monoclonal antibody against the viral glycoprotein E2. Viral entry was dependent on cellular expression of a putative HCV receptor, CD81. HCVcc replication was inhibited by interferon-alpha and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals

Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

Background: The English National Health Service has made a major investment in nine partnerships between higher education institutions and local health services called Collaborations for Leadership in Applied Health Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and implement research through sustained interactions between academics and health services. CLAHRCs provide a natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery. This protocol describes an externally funded evaluation that focuses on implementation mechanisms and processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances. Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth comparative case studies of research implementation using multiple data collection methods including interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of data collection. We will test the wider applicability of emerging findings with a wider community using an interpretative forum. Discussion: The idea that collaboration between academics and services might lead to more applicable health research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g., Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts particularly with respect to integrated stakeholder involvement

Navigating the structural landscape of de Novo α-helical bundles

The association of amphipathic α helices in water leads to α-helical-bundle protein structures. However, the driving force for thisthe hydrophobic effectis not specific and does not define the number or the orientation of helices in the associated state. Rather, this is achieved through deeper sequence-to-structure relationships, which are increasingly being discerned. For example, for one structurally extreme but nevertheless ubiquitous class of bundlethe α-helical coiled coilsrelationships have been established that discriminate between all-parallel dimers, trimers, and tetramers. Association states above this are known, as are antiparallel and mixed arrangements of the helices. However, these alternative states are less well understood. Here, we describe a synthetic-peptide system that switches between parallel hexamers and various up–down–up–down tetramers in response to single-amino-acid changes and solution conditions. The main accessible states of each peptide variant are characterized fully in solution and, in most cases, to high resolution with X-ray crystal structures. Analysis and inspection of these structures helps rationalize the different states formed. This navigation of the structural landscape of α-helical coiled coils above the dimers and trimers that dominate in nature has allowed us to design rationally a well-defined and hyperstable antiparallel coiled-coil tetramer (apCC-Tet). This robust de novo protein provides another scaffold for further structural and functional designs in protein engineering and synthetic biology

De novo protein design:How do we expand into the universe of possible protein structures?

Protein scientists are paving the way to a new phase in protein design and engineering. Approaches and methods are being developed that could allow the design of proteins beyond the confines of natural protein structures. This possibility of designing entirely new proteins opens new questions: What do we build? How do we build into protein-structure space where there are few, if any, natural structures to guide us? To what uses can the resulting proteins be put? And, what, if anything, does this pursuit tell us about how natural proteins fold, function and evolve? We describe the origins of this emerging area of fully de novo protein design, how it could be developed, where it might lead, and what challenges lie ahead

Inheritance of Evolved Glyphosate Resistance in a North Carolina Palmer Amaranth ( Amaranthus palmeri

Inheritance of glyphosate resistance in a Palmer amaranth biotype from North Carolina was studied. Glyphosate rates for 50% survival of glyphosate-resistant (GR) and glyphosate-susceptible (GS) biotypes were 1288 and 58 g ha−1, respectively. These values for F1 progenies obtained from reciprocal crosses (GR×GS and GS×GR were 794 and 501 g ha−1, respectively. Dose response of F1 progenies indicated that resistance was not fully dominant over susceptibility. Lack of significant differences between dose responses for reciprocal F1 families suggested that genetic control of glyphosate resistance was governed by nuclear genome. Analysis of F1 backcross (BC1F1) families showed that 10 and 8 BC1F1 families out of 15 fitted monogenic inheritance at 2000 and 3000 g ha−1 glyphosate, respectively. These results indicate that inheritance of glyphosate resistance in this biotype is incompletely dominant, nuclear inherited, and might not be consistent with a single gene mechanism of inheritance. Relative 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) copy number varied from 22 to 63 across 10 individuals from resistant biotype. This suggested that variable EPSPS copy number in the parents might be influential in determining if inheritance of glyphosate resistance is monogenic or polygenic in this biotype