The CONSORT Statement for randomised controlled clinical trials was one of the first guidelines developed in response to this need 24,25. Since publication, an increasing number of leading journals ...have supported CONSORT as part of their instructions to authors 26,27. ...convincing evidence is emerging that CONSORT improves the quality and transparency of reports of clinical trials 28,29.
Aberrant expression of embryonic epithelial-mesenchymal transition-inducing transcription factors (EMT-TFs) in epithelial cells triggers EMT, neoplastic transformation, stemness, and metastatic ...dissemination. We found that regulation and functions of EMT-TFs are different in malignant melanoma. SNAIL2 and ZEB2 transcription factors are expressed in normal melanocytes and behave as tumor-suppressor proteins by activating an MITF-dependent melanocyte differentiation program. In response to NRAS/BRAF activation, EMT-TF network undergoes a profound reorganization in favor of TWIST1 and ZEB1. This reversible switch cooperates with BRAF in promoting dedifferentiation and neoplastic transformation of melanocytes. We detected EMT-TF reprogramming in late-stage melanoma in association with enhanced phospho-ERK levels. This switch results in E-cadherin loss, enhanced invasion, and constitutes an independent factor of poor prognosis in melanoma patients.
•The EMT-TF reprogramming predicts poor outcome in melanoma patients•The EMT-TF reprogramming is dependent on ERK activity and involves FRA1•ZEB1 and TWIST1 are oncogenic; ZEB2 and SNAIL2 are oncosuppressive in melanoma•The antagonistic properties of EMT-TFs mirror their opposing effects on MITF
Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and ...repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication.
Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were originally commissioned by the ...Department of Health and developed during 1998–2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were first published in January 2001 and updated in 2007. A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective for the prevention of HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. The Department of Health commissioned a review of new evidence and we have updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the epic2 guidelines published in 2007 remain robust, relevant and appropriate, but some guideline recommendations required adjustments to enhance clarity and a number of new recommendations were required. These have been clearly identified in the text. In addition, the synopses of evidence underpinning the guideline recommendations have been updated. These guidelines (epic3) provide comprehensive recommendations for preventing HCAI in hospital and other acute care settings based on the best currently available evidence. National evidence-based guidelines are broad principles of best practice that need to be integrated into local practice guidelines and audited to reduce variation in practice and maintain patient safety. Clinically effective infection prevention and control practice is an essential feature of patient protection. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of health care in NHS hospitals in England can be minimised.
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal ...research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the “ARRIVE Essential 10,” which constitutes the minimum requirement, and the “Recommended Set,” which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal ...research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the ‘ARRIVE Essential 10,’ which constitutes the minimum requirement, and the ‘Recommended Set,’ which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal ...research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the “ARRIVE Essential 10,” which constitutes the minimum requirement, and the “Recommended Set,” which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
With increasing knowledge of the materials science of bulk metallic glasses (BMGs) and improvements in their properties and processing, they have started to become candidate materials for biomedical ...devices. A dichotomy in the types of medical applications has also emerged, in which some families of BMGs are being developed for permanent devices whilst another family – of Mg‐based alloys – is showing promise in bioabsorbable implants. The current status of these metallurgical and technological developments is summarized.
Bulk metallic glasses are becoming candidate materials for biomedical devices, with continuous improvements in their processing and properties. A dichotomy in application types is apparent, in which some families of BMGs are being developed for permanent devices whilst another family – that of Mg‐based alloys – shows promise in bioabsorbable implants. The current status of these metallurgical and technological developments is summarized.
Antimicrobial resistance (AMR) is a serious threat to global public health. WHO emphasises the need for countries to monitor antibiotic consumption to combat AMR. Many low-income and middle-income ...countries (LMICs) lack surveillance capacity; we aimed to use multiple data sources and statistical models to estimate global antibiotic consumption.
In this spatial modelling study, we used individual-level data from household surveys to inform a Bayesian geostatistical model of antibiotic usage in children (aged <5 years) with lower respiratory tract infections in LMICs. Antibiotic consumption data were obtained from multiple sources, including IQVIA, WHO, and the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). The estimates of the antibiotic usage model were used alongside sociodemographic and health covariates to inform a model of total antibiotic consumption in LMICs. This was combined with a single model of antibiotic consumption in high-income countries to produce estimates of antibiotic consumption covering 204 countries and 19 years.
We analysed 209 surveys done between 2000 and 2018, covering 284 045 children with lower respiratory tract infections. We identified large national and subnational variations of antibiotic usage in LMICs, with the lowest levels estimated in sub-Saharan Africa and the highest in eastern Europe and central Asia. We estimated a global antibiotic consumption rate of 14·3 (95% uncertainty interval 13·2–15·6) defined daily doses (DDD) per 1000 population per day in 2018 (40·2 37·2–43·7 billion DDD), an increase of 46% from 9·8 (9·2–10·5) DDD per 1000 per day in 2000. We identified large spatial disparities, with antibiotic consumption rates varying from 5·0 (4·8–5·3) DDD per 1000 per day in the Philippines to 45·9 DDD per 1000 per day in Greece in 2018. Additionally, we present trends in consumption of different classes of antibiotics for selected Global Burden of Disease study regions using the IQVIA, WHO, and ESAC-net input data. We identified large increases in the consumption of fluoroquinolones and third-generation cephalosporins in North Africa and Middle East, and south Asia.
To our knowledge, this is the first study that incorporates antibiotic usage and consumption data and uses geostatistical modelling techniques to estimate antibiotic consumption for 204 countries from 2000 to 2018. Our analysis identifies both high rates of antibiotic consumption and a lack of access to antibiotics, providing a benchmark for future interventions.
Fleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill & Melinda Gates Foundation.
Objectives: We set out to determine the psychometric validation of a disease‐specific health related quality of life instrument for use in chronic rhinosinusitis, the 22 item Sinonasal Outcome Test ...(SNOT‐22), a modification of a pre‐existing instrument, the SNOT‐20.
Design, setting and participants: The National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis was a prospective cohort study collecting data on 3128 adult patients undergoing sinonasal surgery in 87 NHS hospitals in England and Wales. Data were collected preoperatively and at 3 months after surgery, and analysed to determine validity of the SNOT‐22. Test–retest reliability was assessed in a separate cohort of patients in a single centre.
Main outcome measures: The SNOT‐22, a derivative of the SNOT‐20 was the main outcome measure. Patients were also asked to report whether they felt better, the same or worse following surgery. To evaluate the SNOT‐22, the internal consistency, responsiveness, known group differences and validity were analysed.
Results: Preoperative SNOT‐22 scores were completed by 2803 patients. 3‐month postoperative SNOT‐22 scores were available for 2284 patients of all patients who completed a preoperative form (81.5% response rate). The Cronbach’s alpha scores for the SNOT‐22 were 0.91 indicating high internal consistency. The test–retest reliability coefficient was 0.93, indicating high reliability of repeated measures. The SNOT‐22 was able to discriminate between patients known to suffer with chronic rhinosinusitis and a group of healthy controls (P < 0.0001, t = 85.3). It was also able to identify statistically significant differences in sub‐groups of patients with chronic rhinosinusitis. There was a statistically significant (P < 0.0001, t = 39.94) decrease in patient reported SNOT‐22 scores at 3 months. At 3 months the overall effect size in all patients was 0.81, which is considered large. We found the minimally important difference that is the smallest change in SNOT‐22 score that can be detected by a patient, to be 8.9 points.
Conclusions: We have found the SNOT‐22 to be valid and easy to use. It can be used to facilitate routine clinical practice to highlight the impact of chronic rhinosinusitis on the patient’s quality of life, and may also be used to measure the outcome of surgical intervention. The minimally important difference allows us to interpret scores in a clinical context, and may help to improve patient selection for surgery.
PDF
