Detection of Provasopressin in Invasive and Non-invasive (DCIS) Human Breast Cancer Using a Monoclonal Antibody Directed Against the C-terminus (MAG1)

The provasopressin protein (proAVP) is expressed by invasive breast cancer and non-invasive breast cancer, or ductal carcinoma in situ (DCIS). Here we demonstrate the ability of the monoclonal antibody MAG1 directed against the C-terminal end of proAVP to identify proAVP in all cases examined of human invasive cancer and DCIS (35 and 26, respectively). Tissues were chosen to represent a relevant variation in tumor type, grade, patient age, and menopausal status. By comparison, there was 65% positive staining for estrogen receptor, 61% for progesterone receptor, 67% for nuclear p53, and 39% for c-Erb-B2 with the invasive breast cancer sections. Reaction with the normal tissue types examined (67) was restricted to the vasopressinergic magnocellular neurons of the hypothalamus, where provasopressin is normally produced, and the posterior pituitary, where these neurons terminate. The breast epithelial tissue sections on the tissue microarray did not react with MAG1. Previously, we demonstrated that polyclonal antibodies to proAVP detected that protein in all breast cancer samples examined, but there was no reaction with breast tissue containing fibrocystic disease. The results presented here not only expand upon those earlier results, but they also demonstrate the specificity and effectiveness of what may be considered a more clinically-relevant agent. Thus, proAVP appears to be an attractive target for the detection of invasive breast cancer and DCIS, and these results suggest that MAG1 may be a beneficial tool for use in the development of such strategies

Marketing Agency-Client Relationships: Towards A Research Agenda

Purpose - Since agencies play a pivotal role in operationalising marketing strategy, this relationship is central to marketing theory, management and practice. This article presents the first systematic review of the literature relating to the relationships between organisations and their marketing agencies, the agency-client relationship, and presents a concept matrix that identifies the key areas of investigation, and topics where further research would be beneficial. Design/methodology/approach - A systematic review of the literature was performed using key databases and search terms, and filtering on the basis of criteria relating, for example, to relevance and format, to create a core set of refereed articles on the agency-client relationship in the marketing and advertising domains. Bibliographic and thematic analysis was used to profile the literature in the dataset, and to draw out key themes. Findings: The article provides an analysis of the extant knowledge base, including key themes, journals, and research methods. The following themes emerged from the literature, and are used to elaborate further on the existing body of knowledge: conflict, client account management, contracts and agency theory, cultural and international perspectives and co-creation. An agenda for future research is proposed that advocates a focus on theoretical foundations, research strategies, and research topics and themes. Originality/value: This is the first systematic review of the literature on agency- client relationships, which is scattered across disciplines and informed by several theoretical perspectives. Given the increasing complexity of agency-client relationships in the digital age, and increasing need to understand ‘marketing-as- practice’, the coherent overview offered by this article is of particular value for guiding future research

Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required

Methods for high-dimensonal analysis of cells dissociated from cyropreserved synovial tissue

Abstract Background Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples. Methods Multiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq. Results Upon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4+ and CD8+ T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified. Conclusions We have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers

An exploration of research information security data affecting organizational compliance

In this article, data collected from onsite assessments of federal healthcare research programs were reviewed and analyzed. 103 research programs were evaluated for adherence to federal and organizational information security requirements and the data clustered into three primary compliance groupings, technological, procedural, and behavioral. Frequency and cross-tabulation statistics were conducted and chi-square statistics used to test for associations

On your marks, headset, go! Understanding the building blocks of metaverse realms

In 2011, Business Horizons published the social media honeycomb article to help managers and scholars understand what was, then, a new form of media, along with its various platforms and how to engage with and learn to use it. Today, we face similar challenges and opportunities with the metaverse as we try to discover how to attract, enable, serve, and capture value from users in the virtual world. In this article, we introduce the concept of a metaverse realm (i.e., a specific type of metaverse space and community) and present the metaverse honeycomb model to explain the functionalities and affordances for different metaverse realms. We present two applications of the honeycomb model to show how shifting attention to immersive functionalities can characterize various metaverse realms. To conclude, we outline how the model could be used to strategically evaluate metaverse realms in terms of their external fit (i.e., the who-what-how of realms), internal fit (i.e., the trade-offs and synergies of realm functionalities), and life cycles (i.e., roadmapping and directing realm evolution)

On your marks, headset, go! Understanding the building blocks of metaverse realms

In 2011, Business Horizons published the ‘social media honeycomb’ paper to help managers and scholars understand what was, then, a new form of media, its various platforms, and how to engage with it and learn to use it. Today, we face similar challenges and opportunities with the metaverse as we try to discover how to attract, enable, serve and capture value from users in some form of virtual world. In this article, we introduce the concept of a ‘metaverse realm’ (i.e., a specific type of metaverse space and community) and present the metaverse honeycomb model to explain the functionalities and affordances for different metaverse realms. We present two applications of the honeycomb model to show how different attention to immersive functionalities can characterize different metaverse realms. To conclude, we outline how the model could be used to strategically evaluate metaverse realms in terms of their external fit (i.e., the who-what-how of realms), internal fit (i.e., the trade-offs and synergies of realm functionalities), and life-cycles (i.e., roadmapping and directing realm evolution).</p