The SITS-UTMOST: a registry-based prospective study in Europe investigating the impact of regulatory approval of intravenous Actilyse in the extended time window (3–4.5 h) in acute ischaemic stroke

Introduction: The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3–4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. Patients and methods: Inclusion of at least 1000 patients treated within 3–4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3–4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0–2, favourable outcome (mRS 0–1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. Results: 4157 patients from 81 centres in 12 EU countries were entered prospectively (N ¼ 1118 in the 3–4.5 h, N ¼ 3039 in the 0–3 h time window) and 3454 retrospective patients in the 0–3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3–4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3–4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). Discussion: Main weakness is the observational design of the study. Conclusion: This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke

Sanofi in-house medium: Exceeding expectations in cell line development as an alternative to commercially available basal medium

Our current CHO cell line development process has used commercially supplied media for all steps from post-transfection recovery through scale-up and screening of clones. Media alternatives have been developed in house to improve cell culture performance, decrease media cost, and enable modification by Sanofi. A current version of the basal medium has been utilized for cell culture production processes for some early stage development programs. With the goal of utilizing the same media for cell line development and cell culture production, we evaluated this basal medium in different steps of the cell line generation process, with the current (commercial) medium used as the control. Overall, the results demonstrated that the in-house medium met or exceeded the performance of the commercial medium in the cell line development workflow. To assess the in-house basal medium for post-transfection methotrexate (MTX) selection, cell growth and viability were measured during MTX selection, and recombinant protein titers of the MTX-selected pools were assessed. Results show that protein production is comparable between pools selected in the in-house medium versus the control. In addition, use of the in-house medium improved cell growth during selection and decreased the selection timeline by a week. A subsequent MTX kill curve study using the in-house medium showed excellent recovery of transfected cells, even at the higher MTX concentrations used, and high protein titers with less time in selection. Next, the medium was evaluated for single cell cloning in a process using flow cytometry cell sorting to deposit one cell per well in 96-well plates. The initial experiments revealed a minor limitation of the in-house medium for single cell cloning and, based on these results, a cloning version of the basal medium was prepared and tested. Several experiments demonstrated that the cloning version of the in-house medium supported robust cell growth and cloning efficiency that is similar to or better than that obtained with the control. Further studies showed that, for both pools and clones in batch cultures, the in-house medium supports more rapid growth rates and higher cell densities. Experimental results to be presented demonstrate success of the in-house medium in the MTX selection, single cell cloning and outgrowth, and pool and clone screening steps of the cell line development workflow. Furthermore, the advantages of using the in-house medium for pre-master cell banking will be discussed. Proof of concept work from recent cell line generation projects will further demonstrate the utility and advantage of using our in-house medium in the cell line development workflow for new preclinical development programs

A comprehensive platform for quality control of botanical drugs (PhytomicsQC): a case study of Huangqin Tang (HQT) and PHY906

<p>Abstract</p> <p>Background</p> <p>Establishing botanical extracts as globally-accepted polychemical medicines and a new paradigm for disease treatment, requires the development of high-level quality control metrics. Based on comprehensive chemical and biological fingerprints correlated with pharmacology, we propose a general approach called PhytomicsQC to botanical quality control.</p> <p>Methods</p> <p>Incorporating the state-of-the-art analytical methodologies, PhytomicsQC was employed in this study and included the use of liquid chromatography/mass spectrometry (LC/MS) for chemical characterization and chemical fingerprinting, differential cellular gene expression for bioresponse fingerprinting and animal pharmacology for <it>in vivo </it>validation. A statistical pattern comparison method, Phytomics Similarity Index (PSI), based on intensities and intensity ratios, was used to determine the similarity of the chemical and bioresponse fingerprints among different manufactured batches.</p> <p>Results</p> <p>Eighteen batch samples of Huangqin Tang (HQT) and its pharmaceutical grade version (PHY906) were analyzed using the PhytomicsQC platform analysis. Comparative analysis of the batch samples with a clinically tested standardized batch obtained values of PSI similarity between 0.67 and 0.99.</p> <p>Conclusion</p> <p>With rigorous quality control using analytically sensitive and comprehensive chemical and biological fingerprinting, botanical formulations manufactured under standardized manufacturing protocols can produce highly consistent batches of products.</p

OS TRAÇOS DAS NOVAS GERAÇÕES: PRÓS E CONTRAS DA REGULAMENTAÇÃO DAS DITAS “BOAS PRÁTICAS” NA LITERATURA NACIONAL DAS HISTÓRIAS EM QUADRINHOS

O artigo investiga a aplicação de um manual de “boas práticas” prescritas para os produtos editoriais da Mauricio de Sousa Produções (MSP), a serem acatadas pelos profissionais do estúdio. A partir de uma análise textual e imagética das revistas da Turma da Mônica, busca-se compreender as influências internas e externas que corroboram com a evolução dos valores estéticos e morais da obra, em paralelo com a progressão das técnicas de produção gráfica nas últimas décadas. Considerou-se ainda, para efeitos de comparação, outras publicações nacionais como as revistas do Sesinho, através de uma entrevista autoral com o roteirista Alexandre Winck. Com uma base teórica contribuída por Cirne (1972; 1982), Feijó (1967) e Luyten (1989), discute-se os eventuais impactos das delineações éticas e criativas nas histórias em quadrinhos (HQs), identificados por uma perspectiva artística, tecnológica e sociocultural. A pesquisa é propícia para se compreender a influência das intervenções corporativas nos processos comunicacionais pertencente às indústrias criativas, que resultam nas limitações e inovações pautadas pelo viés institucional de uma empresa comercial como a MSP

Genome Wide Association mapping of grain and straw biomass traits in the rice Bengal and Assam Aus Panel (BAAP) grown under alternate wetting and drying and permanently flooded irrigation

The bulk of this work was supported by the Biotechnology and Biological Sciences Research Council mostly from project BB/J003336/1 while a small part of the work by AT was also supported by project BB/N013492/1 (NEWS-India-UK). PR-a is studying for a Ph.D. funded by the Thai Government.Peer reviewedPublisher PD

Modeling Relations Between Event-Related Potential Factors and Broader Versus Narrower Dimensions of Externalizing Psychopathology

The organization of the Hierarchical Taxonomy of Psychopathology (HiTOP) model provides unique opportunities to evaluate whether neural risk measures operate as indicators of broader latent liabilities (e.g., externalizing proneness) or narrower expressions (e.g., antisociality and alcohol abuse). Following this approach, the current study recruited a sample of 182 participants (54% female) who completed measures of externalizing psychopathology (also internalizing) and associated traits. Participants also completed three tasks (Flanker-No Threat, Flanker-Threat, and Go/No-Go tasks) with event-related potential (ERP) measurement. Three variants of two research domain criteria (RDoC)-based neurophysiological indicators—P3 and error-related negativity (ERN)—were extracted from these tasks and used to model two latent ERP factors. Scores on these two ERP factors independently predicted externalizing factor scores when accounting for their covariance with sex—suggesting distinct neural processes contributing to the broad externalizing factor. No predictive relation with the broad internalizing factor was found for either ERP factor. Analyses at the finer-grained level revealed no unique predictive relations of either ERP factor with any specific externalizing symptom variable when accounting for the broad externalizing factor, indicating that ERN and P3 index general liability for problems in this spectrum. Overall, this study provides new insights about neural processes in externalizing psychopathology at broader and narrower levels of the HiTOP hierarchy

TFOS DEWS II Report Executive Summary

This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.TearFilm.org

Avoiding obscure topics and generalising findings produces higher impact research

Much academic research is never cited and may be rarely read, indicating wasted effort from the authors, referees and publishers. One reason that an article could be ignored is that its topic is, or appears to be, too obscure to be of wide interest, even if excellent scholarship produced it. This paper reports a word frequency analysis of 874,411 English article titles from 18 different Scopus natural, formal, life and health sciences categories 2009-2015 to assess the likelihood that research on obscure (rarely researched) topics is less cited. In all categories examined, unusual words in article titles associate with below average citation impact research. Thus, researchers considering obscure topics may wish to reconsider, generalise their study, or to choose a title that reflects the wider lessons that can be drawn. Authors should also consider including multiple concepts and purposes within their titles in order to attract a wider audience

O Brasil e o CARICOM

O estudo das relações entre o Brasil e o CARICOM e outros países caribenhos tem sido historicamente negligenciado pelos analistas brasileiros, o que pode ser comprovado pelo número extremamente pequeno de publicações direcionadas ao assunto. Este artigo tenta proporcionar uma visão geral dos aspectos históricos, diplomáticos, econômicos e políticos, bem como uma perspectiva futura destas relações.The study of the relationship between Brazil and the Caribbean Community, as well as with the Caribbean countries as a whole, have been historically left aside by Brazilian analysts, with an extremely limited amount of publications directed to the subject. This paper hopes to make an overview of historical, diplomatic, economic and political aspects and present events, as well as to offer a perspective of what the future might hold for the relationship between Brazil, the Caribbean Community and its member countries

Neurosurgeons' experiences of conducting and disseminating clinical research in low-income and middle-income countries: a reflexive thematic analysis.

OBJECTIVES: Low-income and-middle-income countries (LMICs) are increasing investment in research and development, yet there remains a paucity of neurotrauma research published by those in LMICs. The aim of this study was to understand neurosurgeons' experiences of, aspirations for, and ability to conduct and disseminate clinical research in LMICs. DESIGN: This was a two-stage inductive qualitative study situated within the naturalistic paradigm. This study committed to an interpretivist way of knowing (epistemology), and considered reality subjective and multiple (ontology). Data collection used online methods and included a web-based survey tool for demographic data, an asynchronous online focus group and follow-up semistructured interviews. Data were analysed using Braun and Clarke's Reflexive Thematic Analysis supported by NVivo V.12. SETTING: LMICs. PARTICIPANTS: In April-July 2020, 26 neurosurgeons from 11 LMICs participated in this study (n=24 in the focus groups, n=20 in follow-up interviews). RESULTS: The analysis gave rise to five themes: The local landscape; creating capacity; reach and impact; collaborative inquiry; growth and sustainability. Each theme contained an inhibitor and stimulus to neurosurgeons conducting and disseminating clinical research, interpreted as 'the neurosurgical research potential in LMICs'. Mentorship, education, infrastructure, impact and engagement were identified as specific accelerators. Whereas lack of generalisability, absence of dissemination and dissemination without peer review may desensitise the impact of research conducted by neurosurgeons. CONCLUSION: The geographical, political and population complexities make research endeavour challenging for neurosurgeons in LMICs. Yet in spite of, and because of, these complexities LMICs provide rich opportunities to advance global neurosurgery. More studies are required to evaluate the specific effects of accelerators of research conducted by neurosurgeons and to understand the effects of desensitisers on high-quality, high-impact clinical research