Systematic assessment of the replicability and generalizability of preclinical findings: Impact of protocol harmonization across laboratory sites.

The influence of protocol standardization between laboratories on their replicability of preclinical results has not been addressed in a systematic way. While standardization is considered good research practice as a means to control for undesired external noise (i.e., highly variable results), some reports suggest that standardized protocols may lead to idiosyncratic results, thus undermining replicability. Through the EQIPD consortium, a multi-lab collaboration between academic and industry partners, we aimed to elucidate parameters that impact the replicability of preclinical animal studies. To this end, 3 experimental protocols were implemented across 7 laboratories. The replicability of results was determined using the distance travelled in an open field after administration of pharmacological compounds known to modulate locomotor activity (MK-801, diazepam, and clozapine) in C57BL/6 mice as a worked example. The goal was to determine whether harmonization of study protocols across laboratories improves the replicability of the results and whether replicability can be further improved by systematic variation (heterogenization) of 2 environmental factors (time of testing and light intensity during testing) within laboratories. Protocols were tested in 3 consecutive stages and differed in the extent of harmonization across laboratories and standardization within laboratories: stage 1, minimally aligned across sites (local protocol); stage 2, fully aligned across sites (harmonized protocol) with and without systematic variation (standardized and heterogenized cohort); and stage 3, fully aligned across sites (standardized protocol) with a different compound. All protocols resulted in consistent treatment effects across laboratories, which were also replicated within laboratories across the different stages. Harmonization of protocols across laboratories reduced between-lab variability substantially compared to each lab using their local protocol. In contrast, the environmental factors chosen to introduce systematic variation within laboratories did not affect the behavioral outcome. Therefore, heterogenization did not reduce between-lab variability further compared to the harmonization of the standardized protocol. Altogether, these findings demonstrate that subtle variations between lab-specific study protocols may introduce variation across independent replicate studies even after protocol harmonization and that systematic heterogenization of environmental factors may not be sufficient to account for such between-lab variation. Differences in replicability of results within and between laboratories highlight the ubiquity of study-specific variation due to between-lab variability, the importance of transparent and fine-grained reporting of methodologies and research protocols, and the importance of independent study replication

Garotas de loja, história social e teoria social [Shop Girls, Social History and Social Theory]

Shop workers, most of them women, have made up a significant proportion of Britain’s labour force since the 1850s but we still know relatively little about their history. This article argues that there has been a systematic neglect of one of the largest sectors of female employment by historians and investigates why this might be. It suggests that this neglect is connected to framings of work that have overlooked the service sector as a whole as well as to a continuing unease with the consumer society’s transformation of social life. One element of that transformation was the rise of new forms of aesthetic, emotional and sexualised labour. Certain kinds of ‘shop girls’ embodied these in spectacular fashion. As a result, they became enduring icons of mass consumption, simultaneously dismissed as passive cultural dupes or punished as powerful agents of cultural destruction. This article interweaves the social history of everyday shop workers with shifting representations of the ‘shop girl’, from Victorian music hall parodies, through modernist social theory, to the bizarre bombing of the Biba boutique in London by the Angry Brigade on May Day 1971. It concludes that progressive historians have much to gain by reclaiming these workers and the service economy that they helped create

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

National Perspectives on Critical and Liberatory Practices in Community Engagement

This keynote presentation featured a dialogue among national leaders in the field of critical and liberatory community engagement, whose work employs community-engaged teaching, research, and economic practices that advance social justice. Their work is described as critical and liberatory because it moves away from traditional community engagement practices toward those that are concerned with social transformation

Between objects and images: drawing diagrams of perception

This research is concerned with the recognition of objects, by which I mean those artefacts made by humans for use in everyday life. To ‘recognize’ something has several possible meanings – to identify it by sight, to see something of your self in it, or to acknowledge that it has special importance or validity. My MFA project explores the territory between these possibilities, in theory and concept, and through drawings on paper and three-dimensional objects. In this paper, objects are considered as an expression of self. I propose that in choosing and arranging the everyday objects in my life, I try to secure some part of my existence or find some objective confirmation of my identity, a tangible point of order to hold on to in the face of an ever-changing universe. In pursuing this theme as a drawing project, I ask: what does it mean to draw these objects, and what does it mean to draw on objects? The psychology of visual perception demonstrates that what we see is a result of what we expect, remember, understand or feel. Looking is active and subjective. Therefore, I suggest that to draw these objects is to examine my self, simultaneously and intuitively mapping the external and internal, objective and subjective. My research moves in this area between seeing and feeling to create diagrams of perception, or drawings about recognition. During this project, the sub-category of objects which I call ‘things’ – those objects that we cannot recognize or name, became central to my work. I argue that our experience of a ‘thing’ is different, more direct and possibly more poetic, than of other objects because it is not mediated by culture or language. The ‘thing’ as an image, occupies a position between abstraction and representation, allowing many interpretations, but refusing certainty. While we look ‘through’ objects to their meanings as signs, things create a still point of doubt and uncertainty. The drawings of and on objects made during my MFA address those moments in life where recognition prompts a search for answers, but no final truth can be determined

On an Average Day in America

This book was completed for Jan Baker\u27s artists\u27 book class.https://digitalcommons.risd.edu/specialcollections_bookmark_culture/1013/thumbnail.jp

Networking resources, owning productivity: a post-development alternative in Mindanao?

This paper explores the practices of one small non-governmental organisation (NGO) in Mindanao working innovatively to challenge power and interests by linking resources to local communities who control their productivity. While this may seem like social capital, I suggest that the agency over production, and the deeply political and ideological nature of the recipient communities, calls for a different reading. The regard for the contextual and contestational politics suggests that a radical alternative is emerging. I use post-development theory to frame the analysis of this example, posing the question: Is this practice a radical alternative to the internationally framed global development discourses, or are we witnessing the reproduction of these discourses in new forms

Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF

Background: Natalizumab for multiple sclerosis (MS) increases the risk of progressive multifocal leukoencephalopathy (PML). Objective: We aimed to assess the effect of natalizumab on cellular composition and functional B cell parameters including patients with natalizumab-associated PML (n=37). Methods: Cellular composition by flow cytometry, levels of immunoglobulin (Ig)G/IgM by immunonephelometry, and oligoclonal bands by isoelectric focusing were studied in blood and cerebrospinal fluid. Results: In MS patients treated with natalizumab without PML (n=59) the proportion of CD19+ B cells was higher in blood, but lower in cerebrospinal fluid compared with MS patients not treated with natalizumab (n=17). The CD4/CD8-ratio in cerebrospinal fluid was lower, and IgG and IgM levels as well as the IgG index dropped in longitudinal samples during natalizumab therapy. Oligoclonal bands persisted, but the total amount of the intrathecally produced IgG fraction, and the polyclonal intrathecal IgG reactivity to measles, rubella, and zoster declined. At the time of diagnosis of PML patients with natalizumab-associated PML had low total IgG levels in blood and cerebrospinal fluid. Conclusions: Natalizumab impacts B and T cell distribution and exerts an inhibitory effect on surrogates of B cell function in periphery and in cerebrospinal fluid, potentially contributing to the increased risk of developing PML