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971.
Carolyn?TarrantEmail authorView authors OrcID profile Barbara?O’Donnell Graham?Martin Julian?Bion Alison?Hunter Kevin?D.?Rooney 《Implementation science : IS》2015,11(1):149
Background
Implementation of the ‘Sepsis Six’ clinical care bundle within an hour of recognition of sepsis is recommended as an approach to reduce mortality in patients with sepsis, but achieving reliable delivery of the bundle has proved challenging. There remains little understanding of the barriers to reliable implementation of bundle components. We examined frontline clinical practice in implementing the Sepsis Six.Methods
We conducted an ethnographic study in six hospitals participating in the Scottish Patient Safety Programme Sepsis collaborative. We conducted around 300 h of non-participant observation in emergency departments, acute medical receiving units and medical and surgical wards. We interviewed a purposive sample of 43 members of hospital staff. Data were analysed using a constant comparative approach.Results
Implementation strategies to promote reliable use of the Sepsis Six primarily focused on education, engaging and motivating staff, and providing prompts for behaviour, along with efforts to ensure that equipment required was readily available. Although these strategies were successful in raising staff awareness of sepsis and engagement with implementation, our study identified that completing the bundle within an hour was not straightforward. Our emergent theory suggested that rather than being an apparently simple sequence of six steps, the Sepsis Six actually involved a complex trajectory comprising multiple interdependent tasks that required prioritisation and scheduling, and which was prone to problems of coordination and operational failures. Interventions that involved allocating specific roles and responsibilities for completing the Sepsis Six in ways that reduced the need for coordination and task switching, and the use of process mapping to identify system failures along the trajectory, could help mitigate against some of these problems.Conclusions
Implementation efforts that focus on individual behaviour change to improve uptake of the Sepsis Six should be supplemented by an understanding of the bundle as a complex trajectory of work in which improving reliability requires attention to coordination of workflow, as well as addressing the mundane problems of interruptions and operational failures that obstruct task completion.972.
973.
974.
Kajala K Brown NJ Williams BP Borrill P Taylor LE Hibberd JM 《The Plant journal : for cell and molecular biology》2012,69(1):47-56
C4 photosynthesis occurs in the most productive crops and vegetation on the planet, and has become widespread because it allows increased rates of photosynthesis compared with the ancestral C3 pathway. Leaves of C4 plants typically possess complicated alterations to photosynthesis, such that its reactions are compartmented between mesophyll and bundle sheath cells. Despite its complexity, the C4 pathway has arisen independently in 62 separate lineages of land plants, and so represents one of the most striking examples of convergent evolution known. We demonstrate that elements in untranslated regions (UTRs) of multiple genes important for C4 photosynthesis contribute to the metabolic compartmentalization characteristic of a C4 leaf. Either the 5′ or the 3′ UTR is sufficient for cell specificity, indicating that functional redundancy underlies this key aspect of C4 gene expression. Furthermore, we show that orthologous PPDK and CA genes from the C3 plant Arabidopsis thaliana are primed for recruitment into the C4 pathway. Elements sufficient for M‐cell specificity in C4 leaves are also present in both the 5′ and 3′ UTRs of these C3A. thaliana genes. These data indicate functional latency within the UTRs of genes from C3 species that have been recruited into the C4 pathway. The repeated recruitment of pre‐existing cis‐elements in C3 genes may have facilitated the evolution of C4 photosynthesis. These data also highlight the importance of alterations in trans in producing a functional C4 leaf, and so provide insight into both the evolution and molecular basis of this important type of photosynthesis. 相似文献
975.
AG Dossetter J Bowyer CR Cook JJ Crawford JE Finlayson NM Heron C Heyes AJ Highton JA Hudson A Jestel S Krapp PA Macfaul TM McGuire AD Morley JJ Morris KM Page LR Ribeiro H Sawney S Steinbacher C Smith 《Bioorganic & medicinal chemistry letters》2012,22(17):5563-5568
The discovery of nitrile compound 4, a potent inhibitor of Cathepsin K (Cat K) with good bioavailability in dog is described. The compound was used to demonstrate target engagement and inhibition of Cat K in an in vivo dog PD model. The margin to hERG ion channel inhibition was deemed too low for a clinical candidate and an optimisation program to find isosteres or substitutions on benzothiazole group led to the discovery of 20, 24 and 27; all three free from hERG inhibition. 相似文献
976.
Holzberger B Strohmeier J Siegmund V Diederichsen U Marx A 《Bioorganic & medicinal chemistry letters》2012,22(9):3136-3139
Fluorescent analogs of the natural nucleobases are widely used as molecular probes for investigating DNA hybridization and topology. In this study the guanosine analogs 8-vinyl- and 8-styryl-2'-deoxyguanosine were synthesized and converted into the corresponding 5'-triphosphates. These C8 modified nucleotides were processed by various DNA polymerases to create fluorescent DNA. Whereas the 8-styryl modified nucleotide somewhat hampers DNA synthesis 8-vinyl-2'-deoxyguanosine is processed by DNA polymerases emphasizing the broad applicability as a molecular probe for fluorescence spectroscopy. 相似文献
977.
Transcranial direct current stimulation (TDCS) is a brain stimulation tool that is portable, painless, inexpensive, apparently safe, and with potential long-term efficacy. Recent results obtained from TDCS experiments offer exciting possibilities for the enhancement and treatment of normal or impaired abilities, respectively. We discuss new neuroethical problems that have emerged from the usage of TDCS, and also focus on one of the most likely future applications of TDCS: enhancing learning and cognition in children with typical and atypical development. 相似文献
978.
Copper transport and accumulation were studied in virgin and lactating C57BL/6 mice, with and without expression of ceruloplasmin
(Cp), to assess the importance of Cp to these processes. One hour after i.p. injection of tracer 64Cu, liver and kidney accounted for 80% of the radioactivity, and mammary gland 1%, while in lactating Cp+/+ mice 2–4 days
post partum, uptake by mammary gland was 9-fold higher and that of liver and other organs was decreased, with 64Cu rapidly appearing in milk. Parallel studies in Cp−/− mice (siblings from same colony) gave virtually identical results.
However, their milk contained less 64Cu, and actual copper contents determined by furnace atomic absorption were less than half those for milk from normal dams.
Liver copper concentrations of pups born to Cp−/− dams also were half those of pups from wild type dams. Copper in pup brains
was unaffected; but iron concentrations were reduced. We conclude that absence of Cp, while not affecting entry of exchangeable
copper from the blood into the mammary gland, does have a significant effect on the availability of this metal to the newborn
through the milk and in the form of stores accumulating in gestation. 相似文献
979.
980.
Cornelis Matijssen M. Cris Silva-Santisteban Isaac M. Westwood Samerene Siddique Vanessa Choi Peter Sheldrake Rob L.M. van Montfort Julian Blagg 《Bioorganic & medicinal chemistry》2012,20(22):6630-6639
Two closely related binding modes have previously been proposed for the ATP-competitive benzimidazole class of checkpoint kinase 2 (CHK2) inhibitors; however, neither binding mode is entirely consistent with the reported SAR. Unconstrained rigid docking of benzimidazole ligands into representative CHK2 protein crystal structures reveals an alternative binding mode involving a water-mediated interaction with the hinge region; docking which incorporates protein side chain flexibility for selected residues in the ATP binding site resulted in a refinement of the water-mediated hinge binding mode that is consistent with observed SAR. The flexible docking results are in good agreement with the crystal structures of four exemplar benzimidazole ligands bound to CHK2 which unambiguously confirmed the binding mode of these inhibitors, including the water-mediated interaction with the hinge region, and which is significantly different from binding modes previously postulated in the literature. 相似文献