The Shadow of a Doubt: a play in three acts by Edith Wharton

No abstract available

The Shadow of a Doubt: discovering a new work by Edith Wharton

No abstract available

Inside help: An integrative review of champions in healthcare-related implementation

Background/aims: The idea that champions are crucial to effective healthcare-related implementation has gained broad acceptance; yet the champion construct has been hampered by inconsistent use across the published literature. This integrative review sought to establish the current state of the literature on champions in healthcare settings and bring greater clarity to this important construct. Methods: This integrative review was limited to research articles in peer-reviewed, English-language journals published from 1980 to 2016. Searches were conducted on the online MEDLINE database via OVID and PubMed using the keyword "champion." Several additional terms often describe champions and were also included as keywords: implementation leader, opinion leader, facilitator, and change agent. Bibliographies of full-text articles that met inclusion criteria were reviewed for additional references not yet identified via the main strategy of conducting keyword searches in MEDLINE. A five-member team abstracted all full-text articles meeting inclusion criteria. Results: The final dataset for the integrative review consisted of 199 unique articles. Use of the term champion varied widely across the articles with respect to topic, specific job positions, or broader organizational roles. The most common method for operationalizing champion for purposes of analysis was the use of a dichotomous variable designating champion presence or absence. Four studies randomly allocated of the presence or absence of champions. Conclusions: The number of published champion-related articles has markedly increased: more articles were published during the last two years of this review (i.e. 2015-2016) than during its first 30 years (i.e. 1980-2009).The number of champion-related articles has continued to increase sharply since the year 2000. Individual studies consistently found that champions were important positive influences on implementation effectiveness. Although few in number, the randomized trials of champions that have been conducted demonstrate the feasibility of using experimental design to study the effects of champions in healthcare

Endoplasmic reticulum stress signalling induces casein kinase 1-dependent formation of cytosolic TDP-43 Inclusions in motor neuron-like cells

YesMotor neuron disease (MND) is a progressive neurodegenerative disease with no effective treatment. One of the principal pathological hallmarks is the deposition of TAR DNA binding protein 43 (TDP-43) in cytoplasmic inclusions. TDP-43 aggregation occurs in both familial and sporadic MND; however, the mechanism of endogenous TDP-43 aggregation in disease is incompletely understood. This study focused on the induction of cytoplasmic accumulation of endogenous TDP-43 in the motor neuronal cell line NSC-34. The endoplasmic reticulum (ER) stressor tunicamycin induced casein kinase 1 (CK1)-dependent cytoplasmic accumulation of endogenous TDP-43 in differentiated NSC-34 cells, as seen by immunocytochemistry. Immunoblotting showed that induction of ER stress had no effect on abundance of TDP-43 or phosphorylated TDP-43 in the NP-40/RIPA soluble fraction. However, there were significant increases in abundance of TDP-43 and phosphorylated TDP-43 in the NP-40/RIPA-insoluble, urea-soluble fraction, including high molecular weight species. In all cases, these increases were lowered by CK1 inhibition. Thus ER stress signalling, as induced by tunicamycin, causes CK1-dependent phosphorylation of TDP-43 and its consequent cytosolic accumulation.Funded by a biomedical research grant from the Motor Neurone Disease Association (ref Rattray/Apr15/837-791). The Bioimaging Facility microscopes used in this study were purchased with grants from BBSRC, Wellcome Trust and the University of Manchester Strategic Fund

Design Construction Networks

This visual essay diagrams a global design construction network that connects architects to migrant construction workers in a direct line. A hypothetical stadium construction site lies in the center; one side maps the movement of a steel truss from design to fabrication to a building site; the other side charts the path of migrant workers as they travel from villages to this construction site. Detailed scenarios outline the work of different actors on both sides, and additionally highlight challenges faced by migrant construction workers and where solutions might intervene. By connecting architects and workers the essay points to visible as well as sometimes hidden economies of architecture, and asks: What are the architects’ ethical responsibilities towards those who erect their buildings around the world? The essay further opens up a theoretical trajectory that seeks to understand the underlying and often unequal systems that structure today’s architecture and construction

Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology.

AIMS: Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for some of the cognitive impairment not fully explained by Alzheimer-type pathology. METHODS: Frontal cortex (Braak stage 0-II) was obtained from the Medical Research Council's Cognitive Function and Ageing Study cohort. Neurones were isolated from eight cases (four high and four low DDR) by laser capture microdissection and changes in the transcriptome identified by microarray analysis. RESULTS: Two thousand three hundred seventy-eight genes were significantly differentially expressed (1690 up-regulated, 688 down-regulated, P < 0.001) in cases with a high neuronal DDR. Functional grouping identified dysregulation of cholesterol biosynthesis, insulin and Wnt signalling, and up-regulation of glycogen synthase kinase 3β. Candidate genes were validated by quantitative real-time polymerase chain reaction. Cerebrospinal fluid levels of 24(S)-hydroxycholesterol associated with neuronal DDR across all Braak stages (rs  = 0.30, P = 0.03). CONCLUSIONS: A persistent neuronal DDR may result in increased cholesterol biosynthesis, impaired insulin and Wnt signalling, and increased GSK3β, thereby contributing to neuronal dysfunction independent of Alzheimer-type pathology in the ageing brain

Multi-tiered external facilitation: the role of feedback loops and tailored interventions in supporting change in a stepped-wedge implementation trial

Background: Facilitation is a complex, relational implementation strategy that guides change processes. Facilitators engage in multiple activities and tailor efforts to local contexts. How this work is coordinated and shared among multiple, external actors and the contextual factors that prompt and moderate facilitators to tailor activities have not been well-described. Methods: We conducted a mixed methods evaluation of a trial to improve the quality of transient ischemic attack care. Six sites in the Veterans Health Administration received external facilitation (EF) before and during a 1-year active implementation period. We examined how EF was employed and activated. Data analysis included prospective logs of facilitator correspondence with sites (160 site-directed episodes), stakeholder interviews (a total of 78 interviews, involving 42 unique individuals), and collaborative call debriefs (n=22) spanning implementation stages. Logs were descriptively analyzed across facilitators, sites, time periods, and activity types. Interview transcripts were coded for content related to EF and themes were identified. Debriefs were reviewed to identify instances of and utilization of EF during site critical junctures. Results: Multi-tiered EF was supported by two groups (site-facing quality improvement [QI] facilitators and the implementation support team) that were connected by feedback loops. Each site received an average of 24 episodes of site-directed EF; most of the EF was delivered by the QI nurse. For each site, site-directed EF frequently involved networking (45%), preparation and planning (44%), process monitoring (44%), and/or education (36%). EF less commonly involved audit and feedback (20%), brainstorming solutions (16%), and/or stakeholder engagement (5%). However, site-directed EF varied widely across sites and time periods in terms of these facilitation types. Site participants recognized the responsiveness of the QI nurse and valued her problem-solving, feedback, and accountability support. External facilitators used monitoring and dialogue to intervene by facilitating redirection during challenging periods of uncertainty about project direction and feasibility for sites. External facilitators, in collaboration with the implementation support team, successfully used strategies tailored to diverse local contexts, including networking, providing data, and brainstorming solutions. Conclusions: Multi-tiered facilitation capitalizing on emergent feedback loops allowed for tailored, site-directed facilitation. Critical juncture cases illustrate the complexity of EF and the need to often try multiple strategies in combination to facilitate implementation progress

Seeding Structures for a Community of Practice Focused on Transient Ischemic Attack (TIA): Implementing Across Disciplines and Waves

Background: The Community of Practice (CoP) model represents one approach to address knowledge management to support effective implementation of best practices. Objective: We sought to identify CoP developmental strategies within the context of a national quality improvement project focused on improving the quality for patients receiving acute transient ischemic attack (TIA) care. Design: Stepped wedge trial. Participants: Multidisciplinary staff at six Veterans Affairs medical facilities. Interventions: To encourage site implementation of a multi-component quality improvement intervention, the trial included strategies to improve the development of a CoP: site kickoff meetings, CoP conference calls, and an interactive website (the "Hub"). Approach: Mixed-methods evaluation included data collected through a CoP attendance log; semi-structured interviews with site participants at 6 months (n = 32) and 12 months (n = 30), and CoP call facilitators (n = 2); and 22 CoP call debriefings. Key results: The critical seeding structures that supported the cultivation of the CoP were the kickoffs which fostered relationships (key to the community element of CoPs) and provided the evidence base relevant to TIA care (key to the domain element of CoPs). The Hub provided the forum for sharing quality improvement plans and other tools which were further highlighted during the CoP calls (key to the practice element of CoPs). CoP calls were curated to create a positive context around participants' work by recognizing team successes. In addition to improving care at their local facilities, the community created a shared set of tools which built on their collective knowledge and could be shared within and outside the group. Conclusions: The PREVENT CoP advanced the mission of the learning healthcare system by successfully providing a forum for shared learning. The CoP was grown through seeding structures that included kickoffs, CoP calls, and the Hub. A CoP expands upon the learning collaborative implementation strategy as an effective implementation practice

Acceptability of a complex team-based quality improvement intervention for transient ischemic attack: a mixed-methods study

Background: The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurologic Symptoms (PREVENT) program was a complex quality improvement (QI) intervention targeting transient ischemic attack (TIA) evidence-based care. The aim of this study was to evaluate program acceptability among the QI teams and factors associated with degrees of acceptability. Methods: QI teams from six Veterans Administration facilities participated in active implementation for a one-year period. We employed a mixed methods study to evaluate program acceptability. Multiple data sources were collected over implementation phases and triangulated for this evaluation. First, we conducted 30 onsite, semi-structured interviews during active implementation with 35 participants at 6 months; 27 interviews with 28 participants at 12 months; and 19 participants during program sustainment. Second, we conducted debriefing meetings after onsite visits and monthly virtual collaborative calls. All interviews and debriefings were audiotaped, transcribed, and de-identified. De-identified files were qualitatively coded and analyzed for common themes and acceptability patterns. We conducted mixed-methods matrix analyses comparing acceptability by satisfaction ratings and by the Theoretical Framework of Acceptability (TFA). Results: Overall, the QI teams reported the PREVENT program was acceptable. The clinical champions reported high acceptability of the PREVENT program. At pre-implementation phase, reviewing quality data, team brainstorming solutions and development of action plans were rated as most useful during the team kickoff meetings. Program acceptability perceptions varied over time across active implementation and after teams accomplished actions plans and moved into sustainment. We observed team acceptability growth over a year of active implementation in concert with the QI team's self-efficacy to improve quality of care. Guided by the TFA, the QI teams' acceptability was represented by the respective seven components of the multifaceted acceptability construct. Conclusions: Program acceptability varied by time, by champion role on QI team, by team self-efficacy, and by perceived effectiveness to improve quality of care aligned with the TFA. A complex quality improvement program that fostered flexibility in local adaptation and supported users with access to data, resources, and implementation strategies was deemed acceptable and appropriate by front-line clinicians implementing practice changes in a large, national healthcare organization