78 research outputs found

    Reporting stAndards for research in PedIatric Dentistry (RAPID):a development protocol

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    Reporting guidelines can improve the quality of reports of research findings. Some specialities in health care however require guidance on areas that are not captured within the existing guidelines, and this is the case for Paediatric Dentistry where no such standards are available to guide the reporting of different types of study designs. The ‘Reporting stAndards for research in PedIatric Dentistry’ (RAPID) group aims to address this need by developing guidelines on reporting elements of research of particular relevance to Paediatric Dentistry. The development of RAPID guidelines will involve a five‐phase process including a Delphi study, which is an explicit consensus development method designed and implemented in accordance with the Guidance on Conducting and REporting DElphi Studies. The guideline development process will be overseen by an Executive Group. Themes specific to areas in Paediatric Dentistry will be selected, and items to be included under each theme will be identified by members of the Executive Group reviewing at least five reports of experimental and analytical study types using existing reporting guidelines. For the Delphi study, the Executive Group will identify an international multidisciplinary RAPID Delphi Group (RDG) of approximately 60 participants including academics, Paediatric Dentists, parents, and other stakeholders. Each item will be evaluated by RDG on clarity using a dichotomous scale (‘well phrased’ or ‘needs revision’) and on suitability for inclusion in the Delphi study using a 9‐point Likert scale (1 = ‘definitely not include’ to 9 = ‘definitely include’). The items will then be included in an online Delphi study of up to four rounds, with participants invited from stakeholder groups across Paediatric Dentistry. Items scored 7 or above by at least 80% of respondents will be included in the checklist and further discussed in a face‐to‐face Delphi consensus meeting. Following this, the Executive Group will finalize the RAPID guidelines. The guidelines will be published in peer‐reviewed scientific journals and disseminated at scientific meetings and conferences. All the outputs from this project will be made freely available on the RAPID website: www.rapid-statement.org

    Reporting stAndards for research in PedIatric Dentistry (RAPID):an expert consensus-based statement

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    Abstract Background Reporting guidelines for different study designs are currently available to report studies with accuracy and transparency. There is a need to develop supplementary guideline items that are specific to areas within Pediatric Dentistry. This study aims to develop Reporting stAndards for research in PedIatric Dentistry (RAPID) guidelines using a pre-defined expert consensus-based Delphi process. Methods The development of the RAPID guidelines was based on the Guidance for Developers of Health Research Reporting Guidelines. Following a comprehensive search of the literature, the Executive Group identified ten themes in Pediatric Dentistry and compiled a draft checklist of items under each theme. The themes were categorized as: General, Oral Medicine, Pathology and Radiology, Children with Special Health Care Needs, Sedation and Hospital Dentistry, Behavior Guidance, Dental Caries, Preventive and Restorative Dentistry, Pulp Therapy, Traumatology, and Interceptive Orthodontics. A RAPID Delphi Group (RDG) was formed comprising of 69 members from 15 countries across six continents. Items were scored using a 9-point rating Likert scale. Items achieving a score of seven and above, marked by at least 70% of RDG members were accepted into the RAPID checklist items. Weighted mean scores were calculated for each item. Statistical significance was set at p < 0.05 and one-way ANOVA was used to calculate the difference in the weighted mean scores between the themes. Results The final RAPID checklist comprised of 128 items that were finalized and approved by the RDG members in the online consensus meeting. The percentage for high scores (scores 7 to 9) ranged from 69.57 to 100% for individual items. The overall weighted mean score of the final items ranged from 7.51 to 8.28 (out of 9) and the difference was statistically significant between the themes (p < 0.05). Conclusions The RAPID statement provides guidance to researchers, authors, reviewers and editors, to ensure that all elements relevant to particular studies are adequately reported

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Volcanic impacts on the Holocene vegetation history of Britain and Ireland? A review and meta-analysis of the pollen evidence

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    Volcanic ash layers show that the products of Icelandic volcanism reached Britain and Ireland many times during the Holocene. Historical records suggest that at least one eruption, that of Laki in a.d. 1783, was associated with impacts on vegetation. These results raise the question: did Icelandic volcanism affect the Holocene vegetation history of Britain and Ireland? Several studies have used pollen data to address this issue but no clear consensus has been reached. We re-analyse the palynological data using constrained ordination with various representations of potential volcanic impacts. We find that the palynological evidence for volcanic impacts on vegetation is weak but suggest that this is a case of absence of evidence and is not necessarily evidence of absence of impact. To increase the chances of identifying volcanic impacts, future studies need to maximise temporal resolution, replicate results, and investigate a greater number of tephras in a broader range of locations, including more studies from lake sediments

    H2A.Z Acidic Patch Couples Chromatin Dynamics to Regulation of Gene Expression Programs during ESC Differentiation

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    The histone H2A variant H2A.Z is essential for embryonic development and for proper control of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions of amino acid sequence of H2A.Z likely determine its functional specialization compared to core histone H2A. For example, H2A.Z contains three divergent residues in the essential C-terminal acidic patch that reside on the surface of the histone octamer as an uninterrupted acidic patch domain; however, we know little about how these residues contribute to chromatin structure and function. Here, we show that the divergent amino acids Gly92, Asp97, and Ser98 in the H2A.Z C-terminal acidic patch (H2A.Z[superscript AP3]) are critical for lineage commitment during ESC differentiation. H2A.Z is enriched at most H3K4me3 promoters in ESCs including poised, bivalent promoters that harbor both activating and repressive marks, H3K4me3 and H3K27me3 respectively. We found that while H2A.Z[superscript AP3] interacted with its deposition complex and displayed a highly similar distribution pattern compared to wild-type H2A.Z, its enrichment levels were reduced at target promoters. Further analysis revealed that H2A.Z[superscript AP3] was less tightly associated with chromatin, suggesting that the mutant is more dynamic. Notably, bivalent genes in H2A.Z[superscript AP3] ESCs displayed significant changes in expression compared to active genes. Moreover, bivalent genes in H2A.Z[superscript AP3] ESCs gained H3.3, a variant associated with higher nucleosome turnover, compared to wild-type H2A.Z. We next performed single cell imaging to measure H2A.Z dynamics. We found that H2A.Z[superscript AP3] displayed higher mobility in chromatin compared to wild-type H2A.Z by fluorescent recovery after photobleaching (FRAP). Moreover, ESCs treated with the transcriptional inhibitor flavopiridol resulted in a decrease in the H2A.Z[superscript AP3] mobile fraction and an increase in its occupancy at target genes indicating that the mutant can be properly incorporated into chromatin. Collectively, our work suggests that the divergent residues in the H2A.Z acidic patch comprise a unique domain that couples control of chromatin dynamics to the regulation of developmental gene expression patterns during lineage commitment.Massachusetts Life Sciences Center (David H. Koch Institute for Integrative Cancer Research at MIT Core Grant P30-CA14051)National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (Grant CBET-0939511)MIT Faculty Start-up FundMassachusetts Institute of Technology. Computational and Systems Biology Initiative (Merck & Co. Postdoctoral Fellowship

    Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial

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    Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

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    Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe
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