168 research outputs found

    Rule-based modelling provides an extendable framework for comparing candidate mechanisms underpinning clathrin polymerisation

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    Abstract Polymerisation of clathrin is a key process that underlies clathrin-mediated endocytosis. Clathrin-coated vesicles are responsible for cell internalization of external substances required for normal homeostasis and life –sustaining activity. There are several hypotheses describing formation of closed clathrin structures. According to one of the proposed mechanisms cage formation may start from a flat lattice buildup on the cellular membrane, which is later transformed into a curved structure. Creation of the curved surface requires rearrangement of the lattice, induced by additional molecular mechanisms. Different potential mechanisms require a modeling framework that can be easily modified to compare between them. We created an extendable rule-based model that describes polymerisation of clathrin molecules and various scenarios of cage formation. Using Global Sensitivity Analysis (GSA) we obtained parameter sets describing clathrin pentagon closure and the emergence/production and closure of large-size clathrin cages/vesicles. We were able to demonstrate that the model can reproduce budding of the clathrin cage from an initial flat array

    An Empirical Analysis of Overlap Publication in Chinese Language and English Research Manuscripts

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    BACKGROUND: There are a number of sound justifications for publishing nearly identical information in Chinese and English medical journals, assuming several conditions are met. Although overlap publication is perceived as undesirable and ethically questionable in Europe and North America, it may serve an important function in some regions where English is not the native tongue. There is no empirical data on the nature and degree of overlap publication in English and Chinese language journals. METHODS/PRINCIPAL FINDINGS: A random sample of 100 English manuscripts from Chinese institutions was selected from PubMed. Key words and institutions were searched in the China National Knowledge Infrastructure, a comprehensive Chinese language research database. Unacknowledged overlap was a priori defined according to International Committee of Medical Journal Editor (ICMJE) guidelines following examination by two individuals. 19% (95% CI 11-27) of English manuscripts from Chinese institutions were found to have substantial overlap with Chinese published work based on full text examination. None of the manuscripts met all of the criteria established by the ICMJE for an acknowledged overlap publication. Individual-level, journal-level, and institutional factors seem to influence overlap publication. Manuscripts associated with an institution outside of China and with more than one institution were significantly less likely to have substantial overlap (p<0.05). CONCLUSIONS/SIGNIFICANCE: Overlap publication was common in this context, but instances of standard ICMJE notations to acknowledge this practice were rare. This research did not cite the identified overlap manuscripts with the hope that these empirical data will inform journal policy changes and structural initiatives to promote clearer policies and manuscripts

    Testing the leadership and organizational change for implementation (LOCI) intervention in substance abuse treatment: A cluster randomized trial study protocol

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    © 2017 The Author(s). Background: Evidence-based practice (EBP) implementation represents a strategic change in organizations that requires effective leadership and alignment of leadership and organizational support across organizational levels. As such, there is a need for combining leadership development with organizational strategies to support organizational climate conducive to EBP implementation. The leadership and organizational change for implementation (LOCI) intervention includes leadership training for workgroup leaders, ongoing implementation leadership coaching, 360° assessment, and strategic planning with top and middle management regarding how they can support workgroup leaders in developing a positive EBP implementation climate. Methods: This test of the LOCI intervention will take place in conjunction with the implementation of motivational interviewing (MI) in 60 substance use disorder treatment programs in California, USA. Participants will include agency executives, 60 program leaders, and approximately 360 treatment staff. LOCI will be tested using a multiple cohort, cluster randomized trial that randomizes workgroups (i.e., programs) within agency to either LOCI or a webinar leadership training control condition in three consecutive cohorts. The LOCI intervention is 12months, and the webinar control intervention takes place in months 1, 5, and 8, for each cohort. Web-based surveys of staff and supervisors will be used to collect data on leadership, implementation climate, provider attitudes, and citizenship. Audio recordings of counseling sessions will be coded for MI fidelity. The unit of analysis will be the workgroup, randomized by site within agency and with care taken that co-located workgroups are assigned to the same condition to avoid contamination. Hierarchical linear modeling (HLM) will be used to analyze the data to account for the nested data structure. Discussion: LOCI has been developed to be a feasible and effective approach for organizations to create a positive climate and fertile context for EBP implementation. The approach seeks to cultivate and sustain both effective general and implementation leadership as well as organizational strategies and support that will remain after the study has ended. Development of a positive implementation climate for MI should result in more positive service provider attitudes and behaviors related to the use of MI and, ultimately, higher fidelity in the use of MI. Trial registration: This study is registered with Clinicaltrials.gov ( NCT03042832 ), 2 February 2017, retrospectively registered

    What is values work? A review of values work in organisations. Kap. 3

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    I: H.Askeland, G. Espedal, B. Jelstad Løvaas & S. Sirris (Eds.), Understanding values work : Institutional perspectives in organizations and leadershipThrough a review of the existing empirical studies and emerging literature on values work in organisations, this paper aims to disambiguate the phenomenon of values work. Values work is understood as ongoing value performances situated in everyday practice in organisations. As such, values work is identified as social and institutional processes of constructing agency, actions and practice in organisations. In this chapter, I show how values work is part of both a performative tradition of process studies and an institutional work tradition that strives to change, disrupt and maintain institutions. Further, I outline how future studies can broaden the field of values work.publishedVersio

    Respectful leadership:Reducing performance challenges posed by leader role incongruence and gender dissimilarity

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    We investigate how respectful leadership can help overcome the challenges for follower performance that female leaders face when working (especially with male) followers. First, based on role congruity theory, we illustrate the biases faced by female leaders. Second, based on research on gender (dis-)similarity, we propose that these biases should be particularly pronounced when working with a male follower. Finally, we propose that respectful leadership is most conducive to performance in female leader–male follower dyads compared with all other gender configurations. A multi-source field study (N = 214) provides partial support for our hypothesis. While our hypothesized effect was confirmed, respectful leadership seems to be generally effective for female leaders irrespective of follower gender, thus lending greater support in this context to the arguments of role congruity rather than gender dissimilarity

    High performing hospitals: a qualitative systematic review of associated factors and practical strategies for improvement.

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    BACKGROUND: High performing hospitals attain excellence across multiple measures of performance and multiple departments. Studying high performing hospitals can be valuable if factors associated with high performance can be identified and applied. Factors leading to high performance are complex and an exclusive quantitative approach may fail to identify richly descriptive or relevant contextual factors. The objective of this study was to undertake a systematic review of qualitative literature to identify methods used to identify high performing hospitals, the factors associated with high performers, and practical strategies for improvement. METHODS: Methods used to collect and summarise the evidence contributing to this review followed the 'enhancing transparency in reporting the synthesis of qualitative research' protocol. Peer reviewed studies were identified through Medline, Embase and Cinahl (Jan 2000-Feb 2014) using specified key words, subject terms, and medical subject headings. Eligible studies required the use of a quantitative method to identify high performing hospitals, and qualitative methods or tools to identify factors associated with high performing hospitals or hospital departments. Title, abstract, and full text screening was undertaken by four reviewers, and inter-rater reliability statistics were calculated for each review phase. Risk of bias was assessed. Following data extraction, thematic syntheses identified contextual factors important for explaining success. Practical strategies for achieving high performance were then mapped against the identified themes. RESULTS: A total of 19 studies from a possible 11,428 were included in the review. A range of process, output, outcome and other indicators were used to identify high performing hospitals. Seven themes representing factors associated with high performance (and 25 sub-themes) emerged from the thematic syntheses: positive organisational culture, senior management support, effective performance monitoring, building and maintaining a proficient workforce, effective leaders across the organisation, expertise-driven practice, and interdisciplinary teamwork. Fifty six practical strategies for achieving high performance were catalogued. CONCLUSIONS: This review provides insights into methods used to identify high performing hospitals, and yields ideas about the factors important for success. It highlights the need to advance approaches for understanding what constitutes high performance and how to harness factors associated with high performance

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
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