A New Space for Patients. How Space Enters Innovation Translation Processes

The contribution takes organizational space to the analytical fore and analyzes the spatial mediation of the translation of patient-centered care. By bridging theories on innovations' translation and the literature on organizational space, the chapter explores how the redesign of healthcare spaces is used to materialize ideas of patient-centredness and what happens when consolidated clinical practices resist and change these spatial translations of an innovation. Specifically the work focuses on a) how patient-centredness translates into the spatial arrangement of the hospital and b) how, in turn, clinical practitioners work with or around the new spatial setup by both taking up the patient-centredness discourse and working around the spatial arrangement

Bone marrow stromal cells in Modic type 1 changes promote neurite outgrowth

The pain in patients with Modic type 1 changes (MC1) is often due to vertebral body endplate pain, which is linked to abnormal neurite outgrowth in the vertebral body and adjacent endplate. The aim of this study was to understand the role of MC1 bone marrow stromal cells (BMSCs) in neurite outgrowth. BMSCs can produce neurotrophic factors, which have been shown to be pro-fibrotic in MC1, and expand in the perivascular space where sensory vertebral nerves are located. The study involved the exploration of the BMSC transcriptome in MC1, co-culture of MC1 BMSCs with the neuroblastoma cell line SH-SY5Y, analysis of supernatant cytokines, and analysis of gene expression changes in co-cultured SH-SY5Y. Transcriptomic analysis revealed upregulated brain-derived neurotrophic factor (BDNF) signaling-related pathways. Co-cultures of MC1 BMSCs with SH-SY5Y cells resulted in increased neurite sprouting compared to co-cultures with control BMSCs. The concentration of BDNF and other cytokines supporting neuron growth was increased in MC1 vs. control BMSC co-culture supernatants. Taken together, these findings show that MC1 BMSCs provide strong pro-neurotrophic cues to nearby neurons and could be a relevant disease-modifying treatment target

Evaluation of the University of Victoria Earth System Climate Model version 2.10 (UVic ESCM 2.10)

The University of Victoria Earth system climate model of intermediate complexity has been a useful tool in recent assessments of long-term climate changes including paleo-climate modelling. Since the last official release of the UVic ESCM 2.9, and the two official updates during the last decade, a lot of model development has taken place in multiple groups. The new version 2.10 of the University of Victoria Earth System Climate Model (UVic ESCM), to be used in the 6th phase of the coupled model intercomparison project (CMIP6), presented here combines and brings together multiple model developments and new components that have taken place since the last official release of the model. To set the foundation of its use, we here describe the UVic ESCM 2.10 and evaluate results from transient historical simulations against observational data. We find that the UVic ESCM 2.10 is capable of reproducing well changes in historical temperature and carbon fluxes, as well as the spatial distribution of many ocean tracers, including temperature, salinity, phosphate and nitrate. This is connected to a good representation of ocean physical properties. For the moment, there remain biases in ocean alkalinity and dissolved inorganic carbon, which will be addressed in the next updates to the model

Intervertebral disc microbiome in Modic changes: Lack of result replication underscores the need for a consensus in low-biomass microbiome analysis

INTRODUCTION The emerging field of the disc microbiome challenges traditional views of disc sterility, which opens new avenues for novel clinical insights. However, the lack of methodological consensus in disc microbiome studies introduces discrepancies. The aims of this study were to (1) compare the disc microbiome of non-Modic (nonMC), Modic type 1 change (MC1), and MC2 discs to findings from prior disc microbiome studies, and (2) investigate if discrepancies to prior studies can be explained with bioinformatic variations. METHODS Sequencing of 16S rRNA in 70 discs (24 nonMC, 25 MC1, and 21 MC2) for microbiome profiling. The experimental setup included buffer contamination controls and was performed under aseptic conditions. Methodology and results were contrasted with previous disc microbiome studies. Critical bioinformatic steps that were different in our best-practice approach and previous disc microbiome studies (taxonomic lineage assignment, prevalence cut-off) were varied and their effect on results were compared. RESULTS There was limited overlap of results with a previous study on MC disc microbiome. No bacterial genera were shared using the same bioinformatic parameters. Taxonomic lineage assignment using "amplicon sequencing variants" was more sensitive and detected 48 genera compared to 22 with "operational taxonomic units" (previous study). Increasing filter cut-off from 4% to 50% (previous study) reduced genera from 48 to 4 genera. Despite these differences, both studies observed dysbiosis with an increased abundance of gram-negative bacteria in MC discs as well as a lower beta-diversity. Cutibacterium was persistently detected in all groups independent of the bioinformatic approach, emphasizing its prevalence. CONCLUSION There is dysbiosis in MC discs. Bioinformatic parameters impact results yet cannot explain the different findings from this and a previous study. Therefore, discrepancies are likely caused by different sample preparations or true biologic differences. Harmonized protocols are required to advance understanding of the disc microbiome and its clinical implications

Role of C-reactive protein in the bone marrow of Modic type 1 changes

Modic type 1 changes (MC1) are vertebral bone marrow lesions and associate with low back pain. Increased serum C-reactive protein (CRP) has inconsistently been associated with MC1. We aimed to provide evidence for a role of CRP in the tissue pathophysiology of MC1 bone marrow. From thirteen MC1 patients undergoing spinal fusion at MC1 levels, vertebral bone marrow aspirates from MC1 and intra-patient control bone marrow were taken. Bone marrow CRP, IL-1, and IL-6 were measured with enzyme-linked immunosorbent assays; lactate dehydrogenase (LDH) was measured with a colorimetric assay. CRP, IL-1, and IL-6 were compared between MC1 and control bone marrow. Bone marrow CRP was correlated with blood CRP and with bone marrow IL-1, IL-6, and LDH. CRP expression by marrow cells was measured with PCR. Increased CRP in MC1 bone marrow (mean difference: +0.22 mg CRP/g protein, 95% CI [-0.04, 0.47], p=0.088) correlated with blood CRP (r=0.69, p=0.018), with bone marrow IL-1β (ρ=0.52, p=0.029) and IL-6 (ρ=0.51, p=0.031). Marrow cells did not express CRP. Increased LDH in MC1 bone marrow (143.1%, 95% CI [110.7%, 175.4%], p=0.014) indicated necrosis. A blood CRP threshold of 3.2 mg/L detected with 100% accuracy increased CRP in MC1 bone marrow. In conclusion, the association of CRP with inflammatory and necrotic changes in MC1 bone marrow provides evidence for a pathophysiological role of CRP in MC1 bone marrow. This article is protected by copyright. All rights reserved

Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates

Background Vertebral endplate signal intensity changes visualized by magnetic resonance imaging termed Modic changes (MC) are highly prevalent in low back pain patients. Interconvertibility between the three MC subtypes (MC1, MC2, MC3) suggests different pathological stages. Histologically, granulation tissue, fibrosis, and bone marrow edema are signs of inflammation in MC1 and MC2. However, different inflammatory infiltrates and amount of fatty marrow suggest distinct inflammatory processes in MC2. Aims The aims of this study were to investigate (i) the degree of bony (BEP) and cartilage endplate (CEP) degeneration in MC2, (ii) to identify inflammatory MC2 pathomechanisms, and (iii) to show that these marrow changes correlate with severity of endplate degeneration. Methods Pairs of axial biopsies (n = 58) spanning the entire vertebral body including both CEPs were collected from human cadaveric vertebrae with MC2. From one biopsy, the bone marrow directly adjacent to the CEP was analyzed with mass spectrometry. Differentially expressed proteins (DEPs) between MC2 and control were identified and bioinformatic enrichment analysis was performed. The other biopsy was processed for paraffin histology and BEP/CEP degenerations were scored. Endplate scores were correlated with DEPs. Results Endplates from MC2 were significantly more degenerated. Proteomic analysis revealed an activated complement system, increased expression of extracellular matrix proteins, angiogenic, and neurogenic factors in MC2 marrow. Endplate scores correlated with upregulated complement and neurogenic proteins. Discussion The inflammatory pathomechanisms in MC2 comprises activation of the complement system. Concurrent inflammation, fibrosis, angiogenesis, and neurogenesis indicate that MC2 is a chronic inflammation. Correlation of endplate damage with complement and neurogenic proteins suggest that complement system activation and neoinnervation may be linked to endplate damage. The endplate-near marrow is the pathomechanistic site, because MC2 occur at locations with more endplate degeneration. Conclusion MC2 are fibroinflammatory changes with complement system involvement which occur adjacent to damaged endplates

Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated

Understanding the role of objects in cross-disciplinary collaboration

In this paper we make a case for the use of multiple theoretical perspectives – theory on boundary objects, epistemic objects, cultural historical activity theory and objects as infrastructure - to understand the role of objects in cross-disciplinary collaboration. A pluralist approach highlights that objects perform at least three types of work in this context: they motivate collaboration; they allow participants to work across different types of boundaries; and they constitute the fundamental infrastructure of the activity. Building on the results of an empirical study we illustrate the insights that each theoretical lens affords into practices of collaboration and develop a novel analytical framework that organizes objects according to the active work they perform. Our framework can help shed new light on the phenomenon, especially with regards the shifting status of objects and sources of conflict (and change) in collaboration. After discussing these novel insights, we outline directions for future research stemming from a pluralist approach. We conclude by noting the managerial implications of our finding

Articulating practice through the interview to the double

The paper aims to realise the critical potential of the practice lens by contributing to the development of a coherent set of methodologies for investigating work and organisational activity. It does so by introducing and critically assessing the "interview to the double" as a method to articulate and represent practice. After briefly illustrating its history and usage, the paper analyses in depth the setting generated by this unusual interview method. It argues that the nature of the encounter produces narratives that are often morally connoted and idealised in character. As a consequence the method is especially useful to capture the going concerns which orient the conduct of the members and the normative and moral dimension of practice. The paper also shows that because it mimics familiar instruction-giving discursive practices, the method constitutes an effective textual device to convey this moral and normative dimension in a way which remains faithful to its situated and contingent nature of practice