Optimising feedback for early career professionals: a scoping review and new framework

Context Meta‐analyses have shown that feedback can be a powerful intervention to increase learning and performance but there is significant variability in impact. New trials are adding little to the question of whether feedback interventions are effective, so the focus now is how to optimise the effect. Early career professionals (ECPs) in busy work environments are a particularly important target group. This literature review aimed to synthesise information to support the optimal design of feedback interventions for ECPs. Methods We undertook a scoping literature review, using search terms such as ‘feedback’ and ‘effectiveness’ in MEDLINE, MEDLINE‐In‐Process, PsycINFO, CINAHL, Education Research Complete, Education Resources Information Center, the Cochrane Database of Systematic Reviews, the Social Sciences Citation Index and Applied Social Sciences Index and Abstracts, to identify empirical studies describing feedback interventions in busy workplaces published in English since 1990. We applied inclusion criteria to identify studies for the mapping stage and extracted key data to inform the next stage. We then selected a subset of papers for the framework development stage, which were subjected to a thematic synthesis by three authors, leading to a new feedback framework and a modified version of feedback intervention theory specifically for ECPs. Results A total of 80 studies were included in the mapping stage, with roughly equal studies from hospital settings and school classrooms, and 17 papers were included in the framework development stage. The feedback framework comprised three main categories (audit, feedback and goal setting) and 22 subcategories. The review highlighted the limited empirical research focusing solely on feedback for ECPs, which was surprising given the particular nuances in feedback for ECPs identified through this study. Conclusions We offer the feedback framework to optimise the design of future feedback interventions for early career professionals and encourage future feedback research to move away from generic models and tailor work to specific target audiences

Freiburg RNA Tools: a web server integrating IntaRNA, ExpaRNA and LocARNA

The Freiburg RNA tools web server integrates three tools for the advanced analysis of RNA in a common web-based user interface. The tools IntaRNA, ExpaRNA and LocARNA support the prediction of RNA–RNA interaction, exact RNA matching and alignment of RNA, respectively. The Freiburg RNA tools web server and the software packages of the stand-alone tools are freely accessible at http://rna.informatik.uni-freiburg.de

Complex architecture and regulated expression of the Sox2ot locus during vertebrate development

The Sox2 gene is a key regulator of pluripotency embedded within an intron of a long noncoding RNA (ncRNA), termed Sox2 overlapping transcript (Sox2ot), which is transcribed in the same orientation. However, this ncRNA remains uncharacterized. Here we show that Sox2ot has multiple transcription start sites associated with genomic features that indicate regulated expression, including highly conserved elements (HCEs) and chromatin marks characteristic of gene promoters. To identify biological processes in which Sox2ot may be involved, we analyzed its expression in several developmental systems, compared to expression of Sox2. We show that Sox2ot is a stable transcript expressed in mouse embryonic stem cells, which, like Sox2, is down-regulated upon induction of embryoid body (EB) differentiation. However, in contrast to Sox2, Sox2ot is up-regulated during EB mesoderm-lineage differentiation. In adult mouse, Sox2ot isoforms were detected in tissues where Sox2 is expressed, as well as in different tissues, supporting independent regulation of expression of the ncRNA. Sox2dot, an isoform of Sox2ot transcribed from a distal HCE located >500 kb upstream of Sox2, was detected exclusively in the mouse brain, with enrichment in regions of adult neurogenesis. In addition, Sox2ot isoforms are transcribed from HCEs upstream of Sox2 in other vertebrates, including in several regions of the human brain. We also show that Sox2ot is dynamically regulated during chicken and zebrafish embryogenesis, consistently associated with central nervous system structures. These observations provide insight into the structure and regulation of the Sox2ot gene, and suggest conserved roles for Sox2ot orthologs during vertebrate development

Statistical properties of thermodynamically predicted RNA secondary structures in viral genomes

By performing a comprehensive study on 1832 segments of 1212 complete genomes of viruses, we show that in viral genomes the hairpin structures of thermodynamically predicted RNA secondary structures are more abundant than expected under a simple random null hypothesis. The detected hairpin structures of RNA secondary structures are present both in coding and in noncoding regions for the four groups of viruses categorized as dsDNA, dsRNA, ssDNA and ssRNA. For all groups hairpin structures of RNA secondary structures are detected more frequently than expected for a random null hypothesis in noncoding rather than in coding regions. However, potential RNA secondary structures are also present in coding regions of dsDNA group. In fact we detect evolutionary conserved RNA secondary structures in conserved coding and noncoding regions of a large set of complete genomes of dsDNA herpesviruses.Comment: 9 pages, 2 figure

Interventions to improve antimicrobial prescribing of doctors in training (IMPACT): a realist review

Background Interventions to improve the antimicrobial prescribing practices of doctors have been implemented widely to curtail the emergence and spread of antimicrobial resistance, but have been met with varying levels of success. Objectives This study aimed to generate an in-depth understanding of how antimicrobial prescribing interventions ‘work’ (or do not work) for doctors in training by taking into account the wider context in which prescribing decisions are enacted. Design The review followed a realist approach to evidence synthesis, which uses an interpretive, theory-driven analysis of qualitative, quantitative and mixed-methods data from relevant studies. Setting Primary and secondary care. Participants Not applicable. Interventions Studies related to antimicrobial prescribing for doctors in training. Main outcome measures Not applicable. Data sources EMBASE (via Ovid), MEDLINE (via Ovid), MEDLINE In-Process and Other Non-Indexed Citations (via Ovid), PsycINFO (via Ovid), Web of Science core collection limited to Science Citation Index Expanded (SCIE) and Conference Proceedings Citation Index – Science (CPCI-S) (via Thomson Reuters), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, the Health Technology Assessment (HTA) database (all via The Cochrane Library), Applied Social Sciences Index and Abstracts (ASSIA) (via ProQuest), Google Scholar (Google Inc., Mountain View, CA, USA) and expert recommendations. Review methods Clearly bounded searches of electronic databases were supplemented by citation tracking and grey literature. Following quality standards for realist reviews, the retrieved articles were systematically screened and iteratively analysed to develop theoretically driven explanations. A programme theory was produced with input from a stakeholder group consisting of practitioners and patient representatives. Results A total of 131 articles were included. The overarching programme theory developed from the analysis of these articles explains how and why doctors in training decide to passively comply with or actively follow (1) seniors’ prescribing habits, (2) the way seniors take into account prescribing aids and seek the views of other health professionals and (3) the way seniors negotiate patient expectations. The programme theory also explains what drives willingness or reluctance to ask questions about antimicrobial prescribing or to challenge the decisions made by seniors. The review outlines how these outcomes result from complex inter-relationships between the contexts of practice doctors in training are embedded in (hierarchical relationships, powerful prescribing norms, unclear roles and responsibilities, implicit expectations about knowledge levels and application in practice) and the mechanisms triggered in these contexts (fear of criticism and individual responsibility, reputation management, position in the clinical team and appearing competent). Drawing on these findings, we set out explicit recommendations for optimal tailoring, design and implementation of antimicrobial prescribing interventions targeted at doctors in training. Limitations Most articles included in the review discussed hospital-based, rather than primary, care. In cases when few data were available to fully capture all the nuances between context, mechanisms and outcomes, we have been explicit about the strength of our arguments. Conclusions This review contributes to our understanding of how antimicrobial prescribing interventions for doctors in training can be better embedded in the hierarchical and interprofessional dynamics of different health-care settings. Future work More work is required to understand how interprofessional support for doctors in training can contribute to appropriate prescribing in the context of hierarchical dynamics

Clusters of internally primed transcripts reveal novel long noncoding RNAs

Non- protein- coding RNAs ( ncRNAs) are increasingly being recognized as having important regulatory roles. Although much recent attention has focused on tiny 22- to 25- nucleotide microRNAs, several functional ncRNAs are orders of magnitude larger in size. Examples of such macro ncRNAs include Xist and Air, which in mouse are 18 and 108 kilobases ( Kb), respectively. We surveyed the 102,801 FANTOM3 mouse cDNA clones and found that Air and Xist were present not as single, full- length transcripts but as a cluster of multiple, shorter cDNAs, which were unspliced, had little coding potential, and were most likely primed from internal adenine- rich regions within longer parental transcripts. We therefore conducted a genome- wide search for regional clusters of such cDNAs to find novel macro ncRNA candidates. Sixty- six regions were identified, each of which mapped outside known protein- coding loci and which had a mean length of 92 Kb. We detected several known long ncRNAs within these regions, supporting the basic rationale of our approach. In silico analysis showed that many regions had evidence of imprinting and/ or antisense transcription. These regions were significantly associated with microRNAs and transcripts from the central nervous system. We selected eight novel regions for experimental validation by northern blot and RT- PCR and found that the majority represent previously unrecognized noncoding transcripts that are at least 10 Kb in size and predominantly localized in the nucleus. Taken together, the data not only identify multiple new ncRNAs but also suggest the existence of many more macro ncRNAs like Xist and Air

The Accelerating Growth of Online Tagging Systems

Research on the growth of online tagging systems not only is interesting in its own right, but also yields insights for website management and semantic web analysis. Traditional models that describing the growth of online systems can be divided between linear and nonlinear versions. Linear models, including the BA model (Brabasi and Albert, 1999), assume that the average activity of users is a constant independent of population. Hence the total activity is a linear function of population. On the contrary, nonlinear models suggest that the average activity is affected by the size of the population and the total activity is a nonlinear function of population. In the current study, supporting evidences for the nonlinear growth assumption are obtained from data on Internet users' tagging behavior. A power law relationship between the number of new tags (F) and the population (P), which can be expressed as F ~ P ^ gamma (gamma > 1), is found. I call this pattern accelerating growth and find it relates the to time-invariant heterogeneity in individual activities. I also show how a greater heterogeneity leads to a faster growth.Comment: 8 pages, 3 figure

Protein-coding and non-coding gene expression analysis in differentiating human keratinocytes using a three-dimensional epidermal equivalent

The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and corniWed layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, diVerentiation, and cell death. To determine genes responsible for initiating and maintaining a corniWed epidermis, organotypic cultures comprised entirely of stratiWed KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array proWle of submerged cultures containing KCs predominantly in a proliferative (relatively undiVerentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct proWle of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, diVerentiation, and cell death. Next, diVerentially expressed microRNAs (miRNAs) and long noncoding (lncRNA) RNAs were identiWed in EEs. Several diVerentially expressed miRNAs were validated by qRT-PCR and Northern blots. miRNAs 203, 205 and Let-7b were up-regulated at early time points (6, 18 and 24 h) but downregulated by 120 h. To study the lncRNA regulation in EEs, we proWled lncRNA expression by microarray and validated the results by qRT-PCR. Although the diVerential expression of several lncRNAs is suggestive of a role in epidermal diVerentiation, their biological functions remain to be elucidated. The current studies lay the foundation for relevant model systems to address such fundamentally important biological aspects of epidermal structure and function in normal and diseased human skin

Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy:a systematic review and meta-analysis

Aim: To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy. Method: MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure. Results: Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity. Interpretation: Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome

Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49). Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens