Implementation of the WHO Surgical Safety Checklist in an Ethiopian Referral Hospital.

BACKGROUND: The WHO Surgical Safety Checklist has a growing evidence base to support its role in improving perioperative safety, although its impact is likely to be directly related to the effectiveness of its implementation. There remains a paucity of documented experience from low-resource settings on Checklist implementation approaches. We report an implementation strategy in a public referral hospital in Addis Ababa, Ethiopia, based on consultation, local leadership, formal introduction, and supported supervision with subsequent audit and feedback. METHODS: Planning, implementation and assessment took place from December 2011 to December 2012. The planning phase, from December 2011 until April 2012, involved a multidisciplinary consultative approach using local leaders, volunteer clinicians, and staff from non-governmental organisations, to draw up a locally agreed and appropriate Checklist. Implementation in April 2012 involved formal teaching and discussion, simulation sessions and role play, with supportive supervision following implementation. Assessment was performed using completed Checklist analysis and staff satisfaction questionnaires at one month and further Checklist analysis combined with semi-structured interviews in December 2012. RESULTS AND DISCUSSION: Checklist compliance rates were 83% for general anaesthetics at one month after implementation, with an overall compliance rate of 65% at eight months. There was a decrease in Checklist compliance over the period of the study to less than 20% by the end of the study period. The 'Sign out' section was reported as being the most difficult section of the Checklist to complete, and was missed completely in 21% of cases. The most commonly missed single item was the team introduction at the start of each case. However, we report high staff satisfaction with the Checklist and enthusiasm for its continued use. CONCLUSION: We report a detailed implementation strategy for introducing the WHO Surgical Safety Checklist to a low-resource setting. We show that this approach can lead to high completion rates and high staff satisfaction, albeit with a drop in completion rates over time. We argue that maximal benefit of the Surgical Safety Checklist is likely to be when it engenders a conversation around patient safety within a department, and when there is local ownership of this process

Understanding the links between hearing impairment and dementia : development and validation of the social and emotional impact of hearing impairment (SEI-HI) questionnaire

Background The links between hearing impairment (HI) and dementia have been well documented, but factors mediating this relationship remain unknown. Major consequences of HI are social and emotional dysfunction, and as the risk of dementia increases linearly with the severity of HI, it is plausible that socio-emotional difficulties may play a role in this association. Objective The aim of this study was to develop and validate a tool to analyse levels of hearing-related disability, to investigate ultimately whether subjective disability contributes to risk of cognitive impairment compared with hearing thresholds alone. Methods Development and validation of the questionnaire, the Social and Emotional Impact of Hearing Impairment (SEI-HI), was conducted in four phases: (1) content; (2) scoring and outcomes; (3) validation; (4) feasibility in a sample of people with cognitive impairment. Results Considerable evidence was found for the internal and external reliability of the tool with high construct validity, concurrent validity and test-retest values of the SEI-HI questionnaire. A feasibility check on 31 patients with mild cognitive impairment or dementia showed the SEI-HI questionnaire was easy to administer and well-received. Conclusion The SEI-HI questionnaire is a relevant instrument to assess hearing-related disability which can be used in people with cognitive decline to assess further impact on risk of developing dementia

Plasma Homeostasis and Cloacal Urine Composition in Crocodylus porosus Caught Along a Salinity Gradient

Juveniles of the Estuarine or Saltwater Crocodile, Crocodylus porosus, maintain both osmotic pressure and plasma electrolyte homeostasis along a salinity gradient from fresh water to the sea. In fresh water (FW) the cloacal urine is a clear solution rich in ammonium and bicarbonate and containing small amounts of white precipitated solids with high concentrations of calcium and magnesium. In salt water (SW) the cloacal urine has a much higher proportion of solids, cream rather than white in colour, which are the major route for excretion of potassium in addition to calcium and magnesium. Neither liquid nor solid fractions of the cloacal urine represent a major route for excretion of sodium chloride. The solids are urates and uric acid, and their production probably constitutes an important strategy for water conservation by C. porosus in SW. These data, coupled with natural history observations and the recent identification of lingual salt glands, contribute to the conclusion that C. porosus is able to live and breed in either fresh or salt water and may be as euryhaline as any reptile

The ethics of digital well-being: a multidisciplinary perspective

This chapter serves as an introduction to the edited collection of the same name, which includes chapters that explore digital well-being from a range of disciplinary perspectives, including philosophy, psychology, economics, health care, and education. The purpose of this introductory chapter is to provide a short primer on the different disciplinary approaches to the study of well-being. To supplement this primer, we also invited key experts from several disciplines—philosophy, psychology, public policy, and health care—to share their thoughts on what they believe are the most important open questions and ethical issues for the multi-disciplinary study of digital well-being. We also introduce and discuss several themes that we believe will be fundamental to the ongoing study of digital well-being: digital gratitude, automated interventions, and sustainable co-well-being

E2F1 drives chemotherapeutic drug resistance via ABCG2

Multidrug resistance is a major barrier against successful chemotherapy, and this has been shown in vitro to be often caused by ATP-binding cassette (ABC) transporters. These transporters are frequently overexpressed in human cancers and confer an adverse prognosis in many common malignancies. The genetic factors, however, that initiate their expression in cancer are largely unknown. Here we report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and specifically activated by the transcription factor E2F1—a factor perturbed in the majority of human cancers. E2F1 regulates ABCG2 expression in multiple cell systems, and, importantly, we have identified a significant correlation between elevated E2F1 and ABCG2 expression in human lung cancers. We show that E2F1 causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2. Furthermore, the E2F1–ABCG2 axis suppresses chemotherapy-induced cell death that can be restored by the inhibition of ABCG2. These findings therefore identify a new axis in multidrug resistance and highlight a radical new function of E2F1 that is relevant to tumor therapy

Two-stage directed self-assembly of a cyclic [3]catenane.

Interlocked molecules possess properties and functions that depend upon their intricate connectivity. In addition to the topologically trivial rotaxanes, whose structures may be captured by a planar graph, the topologically non-trivial knots and catenanes represent some of chemistry's most challenging synthetic targets because of the three-dimensional assembly necessary for their construction. Here we report the synthesis of a cyclic [3]catenane, which consists of three mutually interpenetrating rings, via an unusual synthetic route. Five distinct building blocks self-assemble into a heteroleptic triangular framework composed of two joined Fe(II)3L3 circular helicates. Subcomponent exchange then enables specific points in the framework to be linked together to generate the cyclic [3]catenane product. Our method represents an advance both in the intricacy of the metal-templated self-assembly procedure and in the use of selective imine exchange to generate a topologically complex product.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) and a Marie Curie fellowship for J.J.H. (ITN-2010–264645). The authors thank the Diamond Light Source (UK) for synchrotron beamtime on I19 (MT7984 and MT8464).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nchem.220

Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies

The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contexts are often conserved, while those that vary may indicate functions that are more easily changed or that are no longer required. In analogy to the study of conservation patterns in enzyme sequences and structures, we have examined the patterns of conservation and variation in enzyme function by analyzing graph isomorphisms among enzyme substrates of a large number of enzyme superfamilies. This systematic analysis of substrate substructures establishes the conservation patterns that typify individual superfamilies. Specifically, we determined the chemical substructures that are conserved among all known substrates of a superfamily and the substructures that are reacting in these substrates and then examined the relationship between the two. Across the 42 superfamilies that were analyzed, substantial variation was found in how much of the conserved substructure is reacting, suggesting that superfamilies may not be easily grouped into discrete and separable categories. Instead, our results suggest that many superfamilies may need to be treated individually for analyses of evolution, function prediction, and guiding enzyme engineering strategies. Annotating superfamilies with these conserved and reacting substructure patterns provides information that is orthogonal to information provided by studies of conservation in superfamily sequences and structures, thereby improving the precision with which we can predict the functions of enzymes of unknown function and direct studies in enzyme engineering. Because the method is automated, it is suitable for large-scale characterization and comparison of fundamental functional capabilities of both characterized and uncharacterized enzyme superfamilies

ATP and its N6-substituted analogues: parameterization, molecular dynamics simulation and conformational analysis

In this work we used a combination of classical molecular dynamics and simulated annealing techniques to shed more light on the conformational flexibility of 12 adenosine triphosphate (ATP) analogues in a water environment. We present simulations in AMBER force field for ATP and 12 published analogues [Shah et al. (1997) Proc Natl Acad Sci USA 94: 3565–3570]. The calculations were carried out using the generalized Born (GB) solvation model in the presence of the cation Mg2+. The ion was placed at a close distance (2 Å) from the charged oxygen atoms of the beta and gamma phosphate groups of the −3 negatively charged ATP analogue molecules. Analysis of the results revealed the distribution of inter-proton distances H8–H1′ and H8–H2′ versus the torsion angle ψ (C4–N9-C1′–O4′) for all conformations of ATP analogues. There are two gaps in the distribution of torsion angle ψ values: the first is between −30 and 30 degrees and is described by cis-conformation; and the second is between 90 and 175 degrees, which mostly covers a region of anti conformation. Our results compare favorably with results obtained in experimental assays [Jiang and Mao (2002) Polyhedron 21:435–438]