Simple rules for evidence translation in complex systems: a qualitative study

Background Ensuring patients benefit from the latest medical and technical advances remains a major challenge, with rational-linear and reductionist approaches to translating evidence into practice proving inefficient and ineffective. Complexity thinking, which emphasises interconnectedness and unpredictability, offers insights to inform evidence translation theories and strategies. Drawing on detailed insights into complex micro-systems, this research aimed to advance empirical and theoretical understanding of the reality of making and sustaining improvements in complex healthcare systems. Methods Using analytical auto-ethnography, including documentary analysis and literature review, we assimilated learning from 5 years of observation of 22 evidence translation projects (UK). We used a grounded theory approach to develop substantive theory and a conceptual framework. Results were interpreted using complexity theory and ‘simple rules’ were identified reflecting the practical strategies that enhanced project progress. Results The framework for Successful Healthcare Improvement From Translating Evidence in complex systems (SHIFT-Evidence) positions the challenge of evidence translation within the dynamic context of the health system. SHIFT-Evidence is summarised by three strategic principles, namely (1) ‘act scientifically and pragmatically’ – knowledge of existing evidence needs to be combined with knowledge of the unique initial conditions of a system, and interventions need to adapt as the complex system responds and learning emerges about unpredictable effects; (2) ‘embrace complexity’ – evidence-based interventions only work if related practices and processes of care within the complex system are functional, and evidence-translation efforts need to identify and address any problems with usual care, recognising that this typically includes a range of interdependent parts of the system; and (3) ‘engage and empower’ – evidence translation and system navigation requires commitment and insights from staff and patients with experience of the local system, and changes need to align with their motivations and concerns. Twelve associated ‘simple rules’ are presented to provide actionable guidance to support evidence translation and improvement in complex systems. Conclusion By recognising how agency, interconnectedness and unpredictability influences evidence translation in complex systems, SHIFT-Evidence provides a tool to guide practice and research. The ‘simple rules’ have potential to provide a common platform for academics, practitioners, patients and policymakers to collaborate when intervening to achieve improvements in healthcare

Interactions of the Bacillus subtilis DnaE polymerase with replisomal proteins modulate its activity and fidelity

During Bacillus subtilis replication two replicative polymerases function at the replisome to collectively carry out genome replication. In a reconstituted in vitro replication assay, PolC is the main polymerase while the lagging strand DnaE polymerase briefly extends RNA primers synthesized by the primase DnaG prior to handing-off DNA synthesis to PolC. Here, we show in vivo that (i) the polymerase activity of DnaE is essential for both the initiation and elongation stages of DNA replication, (ii) its error rate varies inversely with PolC concentration, and (iii) its misincorporations are corrected by the mismatch repair system post-replication. We also found that the error rates in cells encoding mutator forms of both PolC and DnaE are significantly higher (up to 15-fold) than in PolC mutants. In vitro, we showed that (i) the polymerase activity of DnaE is considerably stimulated by DnaN, SSB and PolC, (ii) its error-prone activity is strongly inhibited by DnaN, and (iii) its errors are proofread by the 30 . 50 exonuclease activity of PolC in a stable template-DnaE –PolC complex. Collectively our data show that protein –protein interactions within the replisome modulate the activity and fidelity of DnaE, and confirm the prominent role of DnaE during B. subtilis replication

The Effect of Increasing Donor Age on Myocardial Ischemic Tolerance in a Rodent Model of Donation After Circulatory Death.

Hearts from older donors or procured via donation after circulatory death (DCD) can alleviate transplant waitlist; however, these hearts are particularly vulnerable to injury caused by warm ischemic times (WITs) inherent to DCD. This study investigates how the combination of increasing donor age and pharmacologic supplementation affects the ischemic tolerance and functional recovery of DCD hearts and how age impacts cardiac mitochondrial respiratory capacity and oxidative phosphorylation.MethodsWistar rats (12-, 18-, and 24-mo-old) were subjected to DCD with 20-min fixed WIT. Hearts were procured, instrumented onto a Langendorff perfusion circuit, flushed with Celsior preservation solution with or without supplementation (glyceryl trinitrate [GTN]/erythropoietin [EPO]/zoniporide [Z]) and perfused (Krebs-Henseleit buffer, 37°C Langendorff 30-min, working 30-min). Cardiac functional recovery of aortic flow (AF), coronary flow (CF), cardiac output (CO), and lactate dehydrogenase release were measured. Native heart tissue (3-, 12-, and 24-mo) were assessed for mitochondrial respiratory capacity.ResultsUnsupplemented 18- and 24-month DCD hearts showed a 6-fold decrease in AF recovery relative to unsupplemented 12-month DCD hearts. GTN/EPO/Z supplementation significantly increased AF and CO recovery of 18-month DCD hearts to levels comparable to supplemented 12-month hearts; however, GTN/EPO/Z did not improve 24-month DCD heart recovery. Compared to 12-month heart tissue, 24-month hearts exhibited significantly impaired mitochondrial oxygen flux at complex I, II, and uncoupled maximal respiration stage.ConclusionsReduced ischemic tolerance after DCD was associated with increasing age. Pharmacologic supplementation improves functional recovery of rat DCD hearts but only up to age 18 months, possibly attributed to a decline in mitochondrial respiratory capacity with increasing age

Reporting Outcomes of Extremely Preterm Births

Published reports of extremely preterm birth outcomes provide important information to families, clinicians, and others and are widely used to make clinical and policy decisions. Misreporting or misunderstanding of outcome reports may have significant consequences. This article presents 7 recommendations to improve reporting of extremely preterm birth outcomes in both the primary and secondary literature. The recommendations should facilitate clarity in communication about extremely preterm birth outcomes and increase the value of existing and future work in this area

Gill Damage to Atlantic Salmon (Salmo salar) Caused by the Common Jellyfish (Aurelia aurita) under Experimental Challenge

Peer-reviewed. Copyright © 2011 E.J. Baxter et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Over recent decades jellyfish have caused fish kill events and recurrent gill problems in marine-farmed salmonids. Common jellyfish (Aurelia spp.) are among the most cosmopolitan jellyfish species in the oceans, with populations increasing in many coastal areas. The negative interaction between jellyfish and fish in aquaculture remains a poorly studied area of science. Thus, a recent fish mortality event in Ireland, involving Aurelia aurita, spurred an investigation into the effects of this jellyfish on marine-farmed salmon. Methodology/Principal Findings: To address the in vivo impact of the common jellyfish (A. aurita) on salmonids, we exposed Atlantic salmon (Salmo salar) smolts to macerated A. aurita for 10 hrs under experimental challenge. Gill tissues of control and experimental treatment groups were scored with a system that rated the damage between 0 and 21 using a range of primary and secondary parameters. Our results revealed that A. aurita rapidly and extensively damaged the gills of S. salar, with the pathogenesis of the disorder progressing even after the jellyfish were removed. After only 2 hrs of exposure, significant multi-focal damage to gill tissues was apparent. The nature and extent of the damage increased up to 48 hrs from the start of the challenge. Although the gills remained extensively damaged at 3 wks from the start of the challenge trial, shortening of the gill lamellae and organisation of the cells indicated an attempt to repair the damage suffered. Conclusions: Our findings clearly demonstrate that A. aurita can cause severe gill problems in marine-farmed fish. With aquaculture predicted to expand worldwide and evidence suggesting that jellyfish populations are increasing in some areas, this threat to aquaculture is of rising concern as significant losses due to jellyfish could be expected to increase in the future

Folding of small proteins: A matter of geometry?

We review some of our recent results obtained within the scope of simple lattice models and Monte Carlo simulations that illustrate the role of native geometry in the folding kinetics of two state folders.Comment: To appear in Molecular Physic

The formation of professional identity in medical students: considerations for educators

<b>Context</b> Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity – ways of being and relating in professional contexts.<p></p> <b>Objectives</b> This article conceptualises the processes underlying the formation and maintenance of medical students’ professional identity drawing on concepts from social psychology.<p></p> <b>Implications</b> A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.<p></p> <b>Conclusions</b> Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education

The National Women's Health Study: assembly and description of a population-based reproductive cohort

BACKGROUND: Miscarriage is a common event but is remarkably difficult to measure in epidemiological studies. Few large-scale population-based studies have been conducted in the UK. METHODS: This was a population-based two-stage postal survey of reproductive histories of adult women living in the United Kingdom in 2001, sampled from the electronic electoral roll. In Stage 1 a short "screening" questionnaire was sent to over 60,000 randomly selected women in order to identify those aged 55 and under who had ever been pregnant or ever attempted to achieve a pregnancy, from whom a brief reproductive history was requested. Stage 2 involved a more lengthy questionnaire requesting detailed information on every pregnancy (and fertility problems), and questions relating to socio-demographic, behavioural and other factors for the most recent pregnancy in order to examine risk factors for miscarriage. Data on stillbirth, multiple birth and maternal age are compared to national data in order to assess response bias. RESULTS: The response rate was 49% for Stage 1 and 73% for the more targeted Stage 2. A total of 26,050 questionnaires were returned in Stage 1. Of the 17,748 women who were eligible on the grounds of age, 27% reported that they had never been pregnant and had never attempted to conceive a child. The remaining 13,035 women reported a total of 30,661 pregnancies. Comparison of key reproductive indicators (stillbirth and multiple birth rates and maternal age at first birth) with national statistics showed that the data look remarkably similar to the general population. CONCLUSIONS: This study has enabled the assembly of a large population-based dataset of women's reproductive histories which appears unbiased compared to the general UK population and which will enable investigation of hard-to-measure outcomes such as miscarriage and infertility

A rare presentation of Pulmonary Lymphangitic Carcinomatosis in cancer of lip: case report

Squamous cell carcinoma of lip is a common malignancy in Indian subcontinent. Metastatic spread is infrequent. Although advanced tumours spread to lymph nodes in the neck, it does not typically present with lung metastasis or with lymphangitic carcinomatosis. We describe a patient who developed cough and increasing dyspnoea while on treatment for carcinoma of lip. Chest x-ray and computed tomography were consistent with lymphangitic carcinomatosis. Lymphangitic carcinomatosis occurs with many different primary tumours and can rarely occur in oral cancers. This is the first report from carcinoma of lip