Methodologies

方法论
  • 文章类型: Journal Article
    背景:欧洲药品管理局创新工作组(ITF)作为医学和技术开发人员的早期联络点,通过ITF简报会在早期药物开发阶段实现创新。
    目标:为了反思当前的创新速度,并评估ITF利益相关者互动的潜力,对2021年至2022年之间举行的ITF简报会议进行了全面分析,重点是开发商提出的个别问题以及欧洲监管机构提供的相关反馈。
    方法:在ITF简报会议期间提出的问题被提取并分为主要和次要类别,揭示整个医学发展过程中的不同主题,如制造技术,临床前发展,和临床相关问题。
    结果:来自监管机构的积极反馈,他们在85%的答案中给出了初步指导,在20%的答案中提供了具体的例子,并建议在22%的答案中通过额外的监管程序继续讨论。
    结论:此分析框架的内容和在ITF简报会上讨论的主题类型。此外,它描述了提供给医学开发人员的监管反馈类型,并确定了改善这些早期相互作用的潜力。因此,这项分析强调了ITF简报会在促进医学创新中的作用.
    BACKGROUND: The European Medicines Agency Innovation Task Force (ITF) acts as early point of contact for medicine and technology developers to enable innovation during early drug development stages through ITF briefing meetings.
    OBJECTIVE: To reflect on the current pace of innovation and to assess the potential of ITF stakeholder interactions, a comprehensive analysis of the ITF briefing meetings held between 2021 and 2022 was conducted with a focus on individual questions raised by the developers and the related feedback provided by the European regulators.
    METHODS: Questions raised during ITF briefing meetings were extracted and categorised into main and sub-categories, revealing different themes across the whole medicine development process such as manufacturing technologies, pre-clinical developments, and clinically relevant questions.
    RESULTS: There was positive feedback from regulators who gave initial guidance in 85% of the answers, provided concrete examples in 20% of the answers and recommended to continue discussions through additional regulatory procedures in 22% of the answers.
    CONCLUSIONS: This analysis frames the content and the type of topics discussed during ITF briefing meetings. Moreover, it describes the type of regulatory feedback provided to medicine developers and identified potential for improvement of these early interactions. Therefore, this analysis emphasises the role of ITF briefing meetings in fostering innovation in medicine.
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  • 文章类型: Journal Article
    i-基序(iM)是从富含胞嘧啶(C)的序列折叠的四链(四链体)DNA结构。iMs可以在许多不同的体外条件下折叠,这为它们在活细胞中的形成铺平了道路。IBM被认为在各种DNA交易中发挥关键作用,特别是在基因组稳定性的调节中,基因转录,mRNA翻译,DNA复制,端粒和着丝粒功能,和人类疾病。我们总结了用于评估iMs体外折叠的不同技术,并概述了影响其体内形成和稳定性的内部和外部因素。我们描述了iMs可能的生物学相关性,并提出了将其用作生物学靶标的方向。
    An i-motif (iM) is a four-stranded (quadruplex) DNA structure that folds from cytosine (C)-rich sequences. iMs can fold under many different conditions in vitro, which paves the way for their formation in living cells. iMs are thought to play key roles in various DNA transactions, notably in the regulation of genome stability, gene transcription, mRNA translation, DNA replication, telomere and centromere functions, and human diseases. We summarize the different techniques used to assess the folding of iMs in vitro and provide an overview of the internal and external factors that affect their formation and stability in vivo. We describe the possible biological relevance of iMs and propose directions towards their use as target in biology.
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  • 文章类型: Journal Article
    对人种学的理解,和它的目的,不断发展。COVID-19对人种学家构成了重大挑战,特别是那些从事健康相关研究的人。研究人员开发了替代形式的人种学来克服其中一些挑战;我们在2021年开发了适用于人种学的移动即时消息人种学(MIME),以克服我们与医院医生进行研究的限制。然而,使人种学创新对方法论做出重大贡献,它们不应该简单地承担必要性,而是致力于扩大研究范式,授权参与者群体并在本地系统中产生变化,在参与者-合作者和研究人员以及研究过程本身中。在本文中,我们反思我们使用MIME的经验,从2021年6月至12月,与爱尔兰的28名医院医生进行合作远程观察和反思。在回顾了COVID-19的人种学文献和人种学的一般认识论发展之后,我们详细介绍了MIME方法,并说明了MIME如何呈现人种学方法的演变,不仅实际上,而且就其反身性转变而言,它的相互联系和共同创作的基础,以及它推动研究方法变革的能力,参与生活世界和现实世界的改进。
    The understanding of what ethnography looks like, and its purpose, is continuously evolving. COVID-19 posed a significant challenge to ethnographers, particularly those working in health-related research. Researchers have developed alternative forms of ethnography to overcome some of these challenges; we developed the Mobile Instant Messaging Ethnography (MIME) adaptation to ethnography in 2021 to overcome restrictions to our own research with hospital doctors. However, for ethnographic innovations to make a substantial contribution to methodology, they should not simply be borne of necessity, but of a dedicated drive to expand paradigms of research, to empower participant groups and to produce change - in local systems, in participant-collaborators and in researchers and the research process itself. In this paper, we reflect on our experiences using MIME, involving collaborative remote observation and reflection with 28 hospital doctors in Ireland from June to December 2021. After reviewing literature on ethnography in COVID-19 and general epistemological developments in ethnography, we detail the MIME approach and illustrate how MIME presents an evolution of the ethnographic approach, not only practically but in terms of its reflexive shift, its connected and co-creative foundations, and its ability to drive change in research approaches, participant life-worlds and real-world improvement.
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  • 文章类型: Journal Article
    这篇文章有三个民族志,互联,暂时的小插曲讲述了我为一个十几岁的女儿做母亲的生活大流行经历,做社会孤立的家务,和在线教学。这些个人经历位于特定的印度背景下,通过丰富的描述,可以容纳更多的观点。适应莎拉·夏尔马的权力年代和时间政治的概念,我对我的COVID强制的慢时间有问题,并更深入地探索我充满痛苦的COVID时间体验如何与其他人的多个COVID时间相交。我用的是这种方法格式—————————————————————————————————————————————————————————————————————————————————————————————厚厚的描述,和理论化——在微观和大规模层面理解我的大流行经历。
    This essay has three autoethnographic, interconnected, temporal vignettes that narrate my lived pandemic experiences of mothering a teenage daughter, performing socially isolated housework, and teaching online classes. These personal experiences are located in specific Indian contexts through thick descriptions that accommodate more massive perspectives. Adapting Sarah Sharma\'s concepts of power-chronography and temporal politics, I problematize my COVID-enforced slow time, and explore more deeply how my fraught COVID time experiences intersect with the multiple COVID times of others. I use this methodological format-autoethnography, thick description, and theorization-to make sense of my pandemic experiences at both microscopic and massive levels.
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  • 文章类型: Journal Article
    在COVID隔离的5个月中,住在临时住房的手提箱里,出现了无数的分形图案。我不能说如果我通过寻找它们来创造这些模式,或者我看一粒沙子就知道了整个世界。事情的真相是,大规模变革的关键就在我们面前,而是从我们的掌握中溜走。当我们走过这些天,周,和几个月,在差异再次消退之前,我们几乎没有时间。我将此问题作为执行扎根理论的方法来解决。
    In 5 months of COVID isolation, living out of a suitcase in temporary housing, countless fractal patterns emerged. I can\'t say if I created these patterns by looking for them, or that I know the whole world by looking at a grain of sand. The truth of the matter is that it feels like the key for massive scale change is just in front of us, but slipping from our grasp. As we move through these days, weeks, and months, we have very little time before the difference recedes again. I address this matter of concern as a matter of method in performative grounded theory piece.
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  • 文章类型: Journal Article
    这是两种人种学的声音。我们在一个奇怪的时代说话:民主消亡,社会正义死了。很多人死于这种病毒,许多人死于恐惧。我们写信抗议新自由主义和新保守主义的“休克主义”。“我们一起写信抗议破坏性的自我吸收,隔离,和恐惧。这是抗议文本。但是我们不确定我们现在能做什么。
    These are two autoethnographic voices. We speak in a strange time: democracy dies, social justice dies. A lot of people have died of the virus, many die of fear. We write to protest against new neoliberal and neoconservative \"shock doctrine.\" We write together to protest against destructive self-absorption, isolation, and fear. It is protest-text. But we are not sure what we can do now.
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  • 文章类型: Journal Article
    丙二醛是作为多不饱和脂肪酸过氧化的副产物产生的三碳二醛,广泛用作植物中脂质过氧化程度的标志。有几种方法可以量化高等植物中的丙二醛含量,从最简单的,最便宜的,和使用串联质谱法的最复杂的分光光度方法。本章总结了所遵循的方法的优点和局限性,并提供了一些简短的协议,以促进为每种实验条件和应用选择最佳方法。
    Malondialdehyde is a three-carbon dialdehyde produced as a byproduct of polyunsaturated fatty acid peroxidation widely used as a marker of the extent of lipid peroxidation in plants. There are several methodological approaches to quantify malondialdehyde contents in higher plants, ranging from the simplest, cheapest, and quickest spectrophotometric approaches to the more complex ones using tandem mass spectrometry. This chapter summarizes the advantages and limitations of approaches followed and provides brief protocols with some tips to facilitate the selection of the best method for each experimental condition and application.
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  • 文章类型: Editorial
    国际治疗按摩和身体杂志(IJTMB)是通过研究推进治疗按摩和身体专业的专用平台,实践,和教育。在这篇文章中,重点是研究的关键方面,探索各种方法和方法来揭示治疗性按摩和车身研究的复杂性。IJTMB强调多样化研究类型的重要性,仔细考虑使用的方法,并将研究设计和方法的所有决定置于相关的道德考虑范围内。知识翻译的必要性,推动研究人员广泛传播他们的发现,并强调弥合研究与实践之间的差距,以改善该行业和更广泛的社区。IJTMB仍然致力于激励和促进TMB社区内这种充满活力的知识交流,从而推进该领域。
    The International Journal of Therapeutic Massage and Bodywork (IJTMB) serves as a dedicated platform for advancing the therapeutic massage and bodywork profession through research, practice, and education. In this article, the focus is on the critical aspect of research, exploring various methodologies and methods to unveil the complexities within therapeutic massage and bodywork research. The IJTMB emphasizes the importance of diversifying research types, considering carefully the methods used, and placing all decisions for research study design and methods within relevant ethical considerations. The necessity of knowledge translation, pushing researchers to disseminate their findings widely, and bridging the gap between research and practice for the betterment of the profession and the broader community are emphasized. The IJTMB remains committed to inspiring and facilitating this vibrant exchange of knowledge within the TMB community, thereby advancing the field.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    像帕金森病这样的神经系统疾病会引起严重的社会经济问题,目前,只有治疗他们症状的疗法。公认的标志α-突触核蛋白(SYN)富含帕金森病的包涵体特征。我们发现了SYN的一个重要合作伙伴,称为微管蛋白聚合促进蛋白(TPPP),具有重要的生理和病理活动,如微管网络的调节和SYN聚集的促进。TPPP在帕金森病中的作用在研究中经常被忽视,我们在这里试图补救。在正常的大脑中,SYN和TPPP在神经元和少突胶质细胞中内源性表达,分别,while,在帕金森症的早期阶段,在两种细胞类型中都发现了这些蛋白质的可溶性异源缔合。这些蛋白质的细胞间传递,这是疾病进展的核心,为特定的药物靶向提供了独特的情况。用于干预和发现生物标志物的不同策略包括(i)SYN-TPPP异源复合物的界面靶向;(ii)使用PROTAC技术的SYN和/或TPPP的蛋白水解降解;和(iii)通过miRNA技术消耗蛋白质。我们还讨论了SYN和TPPP在神经元和少突胶质细胞表型稳定中的潜在作用。
    Neurological disorders such as Parkinsonism cause serious socio-economic problems as there are, at present, only therapies that treat their symptoms. The well-established hallmark alpha-synuclein (SYN) is enriched in the inclusion bodies characteristic of Parkinsonism. We discovered a prominent partner of SYN, termed Tubulin Polymerization Promoting Protein (TPPP), which has important physiological and pathological activities such as the regulation of the microtubule network and the promotion of SYN aggregation. The role of TPPP in Parkinsonism is often neglected in research, which we here attempt to remedy. In the normal brain, SYN and TPPP are expressed endogenously in neurons and oligodendrocytes, respectively, whilst, at an early stage of Parkinsonism, soluble hetero-associations of these proteins are found in both cell types. The cell-to-cell transmission of these proteins, which is central to disease progression, provides a unique situation for specific drug targeting. Different strategies for intervention and for the discovery of biomarkers include (i) interface targeting of the SYN-TPPP hetero-complex; (ii) proteolytic degradation of SYN and/or TPPP using the PROTAC technology; and (iii) depletion of the proteins by miRNA technology. We also discuss the potential roles of SYN and TPPP in the phenotype stabilization of neurons and oligodendrocytes.
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