RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing.

RNA splicing is an important biological process associated with cancer initiation and progression. However, the contribution of alternative splicing to pancreatic cancer (PDAC) development is not well understood. Here, we identify an enrichment of RNA binding proteins (RBPs) involved in splicing regulation linked to PDAC progression from a forward genetic screen using Sleeping Beauty insertional mutagenesis in a mouse model of pancreatic cancer. We demonstrate downregulation of RBFOX2, an RBP of the FOX family, promotes pancreatic cancer progression and liver metastasis. Specifically, we show RBFOX2 regulates exon splicing events in transcripts encoding proteins involved in cytoskeletal remodeling programs. These exons are differentially spliced in PDAC patients, with enhanced exon skipping in the classical subtype for several RBFOX2 targets. RBFOX2 mediated splicing of ABI1, encoding the Abelson-interactor 1 adapter protein, controls the abundance and localization of ABI1 protein isoforms in pancreatic cancer cells and promotes the relocalization of ABI1 from the cytoplasm to the periphery of migrating cells. Using splice-switching antisense oligonucleotides (AONs) we demonstrate the ABI1 ∆Ex9 isoform enhances cell migration. Together, our data identify a role for RBFOX2 in promoting PDAC progression through alternative splicing regulation.

Push notifications for critical labs results: a pilot study in the intensive care unit (ICU).

Objective: We developed a push notification allowing for an electronic acknowledgment of critical lab results to providers in the intensive care unit. Materials and Methods: This project was conducted over a 3-month period at a large academic safety net hospital. A push notification and acknowledgment system were created to comply with the existing critical results notification requirements. We monitored the number of acknowledged results, time to acknowledgment, and lab type. Results: Prior to the push notification, lab services paged the provider. This resulted in many critical lab results relayed to the clinician beyond the expected 10-minute window. With the push notification workflow, we found that, during the 3-month period, 82, or 5.8%, of the 1414 results were acknowledged. This represented 82 less pages/calls lab services had to make. Discussion: The push notification alert was easy to use and there was quicker results notification when acknowledged. There were limitations due to hand-offs for clinicians and some were not familiar with the mobile technology and the electronic acknowledgment. Conclusions: Although the acknowledgment rate was low, every electronic acknowledgment saved lab service technicians an average of 10 minutes compared to the existing workflow. As familiarity with the technology and workflow increases, this novel form of communication has the potential to have significant cost savings for lab services, in addition to efficiency gains for lab, clinicians, and more timely care. The integration of health information technology and push notification of critical labs should be the focus of investigation for further future research.

Transposon Mutagenesis Reveals RBMS3 Silencing as a Promoter of Malignant Progression of BRAFV600E-Driven Lung Tumorigenesis.

Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment of patients with FDA-approved inhibitors of BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression of BRAFV600E in the lung epithelium initiates growth of benign lung tumors that, without additional genetic alterations, rarely progress to malignant lung adenocarcinoma. To identify genes that cooperate with BRAFV600E for malignant progression, we used Sleeping Beauty-mediated transposon mutagenesis, which dramatically accelerated the emergence of lethal lung cancers. Among the genes identified was Rbms3, which encodes an RNA-binding protein previously implicated as a putative tumor suppressor. Silencing of RBMS3 via CRISPR/Cas9 gene editing promoted growth of BRAFV600E lung organoids and promoted development of malignant lung cancers with a distinct micropapillary architecture in BRAFV600E and EGFRL858R GEM models. BRAFV600E/RBMS3Null lung tumors displayed elevated expression of Ctnnb1, Ccnd1, Axin2, Lgr5, and c-Myc mRNAs, suggesting that RBMS3 silencing elevates signaling through the WNT/ß-catenin signaling axis. Although RBMS3 silencing rendered BRAFV600E-driven lung tumors resistant to the effects of dabrafenib plus trametinib, the tumors were sensitive to inhibition of porcupine, an acyltransferase of WNT ligands necessary for their secretion. Analysis of The Cancer Genome Atlas patient samples revealed that chromosome 3p24, which encompasses RBMS3, is frequently lost in non-small cell lung cancer and correlates with poor prognosis. Collectively, these data reveal the role of RBMS3 as a lung cancer suppressor and suggest that RBMS3 silencing may contribute to malignant NSCLC progression. SIGNIFICANCE: Loss of RBMS3 cooperates with BRAFV600E to induce lung tumorigenesis, providing a deeper understanding of the molecular mechanisms underlying mutant BRAF-driven lung cancer and potential strategies to more effectively target this disease.

Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression.

The systematic identification of genetic events driving cellular transformation and tumor progression in the absence of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified both known tumor suppressor genes and novel oncogenic drivers of cuSCC. Functional analysis confirms an oncogenic role for the ZMIZ genes, and tumor suppressive roles for KMT2C, CREBBP and NCOA2, in the initiation or progression of human cuSCC. Taken together, our in vivo screen demonstrates an extremely heterogeneous genetic landscape of cuSCC initiation and progression, which can be harnessed to better understand skin oncogenic etiology and prioritize therapeutic candidates.

HNRNPM controls circRNA biogenesis and splicing fidelity to sustain cancer cell fitness.

High spliceosome activity is a dependency for cancer cells, making them more vulnerable to perturbation of the splicing machinery compared to normal cells. To identify splicing factors important for prostate cancer (PCa) fitness, we performed pooled shRNA screens in vitro and in vivo. Our screens identified heterogeneous nuclear ribonucleoprotein M (HNRNPM) as a regulator of PCa cell growth. RNA- and eCLIP-sequencing identified HNRNPM binding to transcripts of key homeostatic genes. HNRNPM binding to its targets prevents aberrant exon inclusion and backsplicing events. In both linear and circular mis-spliced transcripts, HNRNPM preferentially binds to GU-rich elements in long flanking proximal introns. Mimicry of HNRNPM-dependent linear-splicing events using splice-switching-antisense-oligonucleotides was sufficient to inhibit PCa cell growth. This suggests that PCa dependence on HNRNPM is likely a result of mis-splicing of key homeostatic coding and non-coding genes. Our results have further been confirmed in other solid tumors. Taken together, our data reveal a role for HNRNPM in supporting cancer cell fitness. Inhibition of HNRNPM activity is therefore a potential therapeutic strategy in suppressing growth of PCa and other solid tumors.

Promoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation.

A central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor gene mutations driving cellular transformation and tumor progression in the absence of oncogenic driver mutation(s). Multiple in vitro and in vivo gene inactivation screens have enhanced our understanding of the tumor suppressor gene landscape in various cancers. However, these studies are limited to single or combination gene effects, specific organs, or require sensitizing mutations. In this study, we developed and utilized a Sleeping Beauty transposon mutagenesis system that functions only as a gene trap to exclusively inactivate tumor suppressor genes. Using whole body transposon mobilization in wild type mice, we observed that cumulative gene inactivation can drive tumorigenesis of solid cancers. We provide a quantitative landscape of the tumor suppressor genes inactivated in these cancers and show that, despite the absence of oncogenic drivers, these genes converge on key biological pathways and processes associated with cancer hallmarks.

A mixed methods investigation of an online intervention to facilitate student midwives' engagement in effective conversations about weight-related behaviour change with pregnant women.

OBJECTIVE: (1) To identify whether an online training intervention could increase midwifery students' knowledge of behaviour change techniques (BCTs) and intentions to use them in practice. (2) To identify students' views and current experiences of talking to women about weight-related behaviour change. DESIGN: Mixed methods study involving pre- and post-training assessments, and qualitative interviews with midwifery students. SETTING: Online training course delivered at a University in the North of England, UK. PARTICIPANTS: Midwifery students in the third year of their undergraduate degree during 2015-2016. INTERVENTION: Online training focused on equipping students with knowledge of theoretically-informed BCTs, and the skills to use them opportunistically in existing practice settings. MEASUREMENTS: Likelihood of discussing obesity with women was assessed via a 12-item, 7-point Likert scale assessing students' attitudes, subjective norms, perceived behavioural control, and intentions. A 14-item checklist was used to assess BCT knowledge whereby students selected recognised BCTs (of 7 correct, 7 false). Students' views and experiences of current practice was explored through in-depth, semi-structured one-on-one interviews with a member of the research team. FINDINGS: Students' subjective norms, perceived behavioural control, and knowledge of BCTs increased post-training but intention and attitudes did not. Interviews revealed three themes accounting for students experiences and views of behaviour change practice: (1) 'How training fits with current encounters with maternal obesity in midwifery training' (2) 'TEnT PEGS prepares students for practice', and (3) 'Value of tailored training'. KEY CONCLUSIONS: Online BCT training can improve the midwifery students' confidence, knowledge and beliefs that this is part of their role. They also reported finding the training helpful in better preparing them for this challenging element of their routine practice. IMPLICATIONS FOR PRACTICE: Online BCT training can be used to prepare undergraduate midwifery students for practice.

SB Driver Analysis: a Sleeping Beauty cancer driver analysis framework for identifying and prioritizing experimentally actionable oncogenes and tumor suppressors.

Cancer driver prioritization for functional analysis of potential actionable therapeutic targets is a significant challenge. Meta-analyses of mutated genes across different human cancer types for driver prioritization has reaffirmed the role of major players in cancer, including KRAS, TP53 and EGFR, but has had limited success in prioritizing genes with non-recurrent mutations in specific cancer types. Sleeping Beauty (SB) insertional mutagenesis is a powerful experimental gene discovery framework to define driver genes in mouse models of human cancers. Meta-analyses of SB datasets across multiple tumor types is a potentially informative approach to prioritize drivers, and complements efforts in human cancers. Here, we report the development of SB Driver Analysis, an in-silico method for defining cancer driver genes that positively contribute to tumor initiation and progression from population-level SB insertion data sets. We demonstrate that SB Driver Analysis computationally prioritizes drivers and defines distinct driver classes from end-stage tumors that predict their putative functions during tumorigenesis. SB Driver Analysis greatly enhances our ability to analyze, interpret and prioritize drivers from SB cancer datasets and will continue to substantially increase our understanding of the genetic basis of cancer.

About Politeness, Face, and Feedback: Exploring Resident and Faculty Perceptions of How Institutional Feedback Culture Influences Feedback Practices.

PURPOSE: To explore resident and faculty perspectives on what constitutes feedback culture, their perceptions of how institutional feedback culture (including politeness concepts) might influence the quality and impact of feedback, feedback seeking, receptivity, and readiness to engage in bidirectional feedback. METHOD: Using a constructivist grounded theory approach, five focus group discussions with internal medicine residents, three focus group discussions with general medicine faculty, and eight individual interviews with subspecialist faculty were conducted at Brigham and Women's Hospital between April and December 2016. Discussions and interviews were audiotaped and transcribed verbatim; concurrent data collection and analysis were performed using the constant comparative approach. Analysis was considered through the lens of politeness theory and organizational culture. RESULTS: Twenty-nine residents and twenty-two general medicine faculty participated in focus group discussions, and eight subspecialty faculty participated in interviews. The institutional feedback culture was described by participants as (1) a culture of politeness, in which language potentially damaging to residents' self-esteem was discouraged; and (2) a culture of excellence, in which the institution's outstanding reputation and pedigree of trainees inhibited constructive feedback. Three key themes situated within this broader cultural context were discovered: normalizing constructive feedback to promote a culture of growth, overcoming the mental block to feedback seeking, and hierarchical culture impeding bidirectional feedback. CONCLUSIONS: An institutional feedback culture of excellence and politeness may impede honest, meaningful feedback and may impact feedback seeking, receptivity, and bidirectional feedback exchanges. It is essential to understand the institutional feedback culture before it can be successfully changed.

The R2C2 Model in Residency Education: How Does It Foster Coaching and Promote Feedback Use?

PURPOSE: The authors previously developed and tested a reflective model for facilitating performance feedback for practice improvement, the R2C2 model. It consists of four phases: relationship building, exploring reactions, exploring content, and coaching. This research studied the use and effectiveness of the model across different residency programs and the factors that influenced its effectiveness and use. METHOD: From July 2014-October 2016, case study methodology was used to study R2C2 model use and the influence of context on use within and across five cases. Five residency programs (family medicine, psychiatry, internal medicine, surgery, and anesthesia) from three countries (Canada, the United States, and the Netherlands) were recruited. Data collection included audiotaped site assessment interviews, feedback sessions, and debriefing interviews with residents and supervisors, and completed learning change plans (LCPs). Content, thematic, template, and cross-case analysis were conducted. RESULTS: An average of nine resident-supervisor dyads per site were recruited. The R2C2 feedback model, used with an LCP, was reported to be effective in engaging residents in a reflective, goal-oriented discussion about performance data, supporting coaching, and enabling collaborative development of a change plan. Use varied across cases, influenced by six general factors: supervisor characteristics, resident characteristics, qualities of the resident-supervisor relationship, assessment approaches, program culture and context, and supports provided by the authors. CONCLUSIONS: The R2C2 model was reported to be effective in fostering a productive, reflective feedback conversation focused on resident development and in facilitating collaborative development of a change plan. Factors contributing to successful use were identified.

Obstetric and gynecologic ultrasound curriculum and competency assessment in residency training programs: consensus report.

Ultrasound imaging has become integral to the practice of obstetrics and gynecology. With increasing educational demands and limited hours in residency programs, dedicated time for training and achieving competency in ultrasound has diminished substantially. The American Institute of Ultrasound in Medicine assembled a multisociety task force to develop a consensus-based, standardized curriculum and competency assessment tools for obstetric and gynecologic ultrasound training in residency programs. The curriculum and competency assessment tools were developed based on existing national and international guidelines for the performance of obstetric and gynecologic ultrasound examinations and thus are intended to represent the minimum requirement for such training. By expert consensus, the curriculum was developed for each year of training, criteria for each competency assessment image were generated, the pass score was established at, or close to, 75% for each, and obtaining a set of 5 ultrasound images with pass score in each was deemed necessary for attaining each competency. Given the current lack of substantial data on competency assessment in ultrasound training, the task force expects that the criteria set forth in this document will evolve with time. The task force also encourages use of ultrasound simulation in residency training and expects that simulation will play a significant part in the curriculum and the competency assessment process. Incorporating this training curriculum and the competency assessment tools may promote consistency in training and competency assessment, thus enhancing the performance and diagnostic accuracy of ultrasound examination in obstetrics and gynecology.

Obstetric and Gynecologic Ultrasound Curriculum and Competency Assessment in Residency Training Programs: Consensus Report.

Ultrasound imaging has become integral to the practice of obstetrics and gynecology. With increasing educational demands and limited hours in residency programs, dedicated time for training and achieving competency in ultrasound has diminished substantially. The American Institute of Ultrasound in Medicine assembled a multisociety task force to develop a consensus-based, standardized curriculum and competency assessment tools for obstetric and gynecologic ultrasound training in residency programs. The curriculum and competency assessment tools were developed based on existing national and international guidelines for the performance of obstetric and gynecologic ultrasound examinations and thus are intended to represent the minimum requirement for such training. By expert consensus, the curriculum was developed for each year of training, criteria for each competency assessment image were generated, the pass score was established at, or close to, 75% for each, and obtaining a set of 5 ultrasound images with pass score in each was deemed necessary for attaining each competency. Given the current lack of substantial data on competency assessment in ultrasound training, the task force expects that the criteria set forth in this document will evolve with time. The task force also encourages use of ultrasound simulation in residency training and expects that simulation will play a significant part in the curriculum and the competency assessment process. Incorporating this training curriculum and the competency assessment tools may promote consistency in training and competency assessment, thus enhancing the performance and diagnostic accuracy of ultrasound examination in obstetrics and gynecology.

SBCDDB: Sleeping Beauty Cancer Driver Database for gene discovery in mouse models of human cancers.

Large-scale oncogenomic studies have identified few frequently mutated cancer drivers and hundreds of infrequently mutated drivers. Defining the biological context for rare driving events is fundamentally important to increasing our understanding of the druggable pathways in cancer. Sleeping Beauty (SB) insertional mutagenesis is a powerful gene discovery tool used to model human cancers in mice. Our lab and others have published a number of studies that identify cancer drivers from these models using various statistical and computational approaches. Here, we have integrated SB data from primary tumor models into an analysis and reporting framework, the Sleeping Beauty Cancer Driver DataBase (SBCDDB, http://sbcddb.moffitt.org), which identifies drivers in individual tumors or tumor populations. Unique to this effort, the SBCDDB utilizes a single, scalable, statistical analysis method that enables data to be grouped by different biological properties. This allows for SB drivers to be evaluated (and re-evaluated) under different contexts. The SBCDDB provides visual representations highlighting the spatial attributes of transposon mutagenesis and couples this functionality with analysis of gene sets, enabling users to interrogate relationships between drivers. The SBCDDB is a powerful resource for comparative oncogenomic analyses with human cancer genomics datasets for driver prioritization.

Adolescent interviewing skills: effect of feedback.

BACKGROUND: Communicating with adolescent patients can be challenging. Our study assessed the effect of structured feedback following a standardised patient (SP) encounter on postgraduate year-1 (PGY1) residents' adolescent-specific communication skills. Communicating with adolescent patients can be challenging METHODS: A two-group, prospective, double-blind randomised control study design was employed. Measures were taken before and after the intervention. PGY1 residents conducted a 30-minute interview with an SP adolescent-mother pair, who then individually scored the resident's performance using the validated Structured Communication Adolescent Guide (SCAG). PGY1s were randomised to receive either structured feedback following the interview (feedback group) or no feedback (no feedback group). All residents completed a second interview 4-6 weeks later. Scores were analysed using unpaired t-tests. RESULTS: Thirty-eight residents completed both interviews. The mean total-item and mean global scores for the first interview did not differ significantly between the feedback (n = 21) and no-feedback group (n = 17). The mean total-item scores for the feedback group [first interview: 34.19 ± 10.19 (adolescent); 36.33 ± 9.77 (mother)] improved significantly for the second interview [45.17 ± 6.22 (adolescent); 44.71 ± 6.72 (mother); p = 0.002 and 0.003, respectively]. The mean global scores also improved significantly from the first interview [27.00 ± 6.49 (adolescent); 27.47 ± 6.50 (mother)] to the second interview [34.05 ± 3.30 (adolescent); 31.19 ± 3.85 (mother); p = 0.001 and 0.03, respectively]. No significant improvement in the mean total-item or mean global rating was observed in the no feedback group. CONCLUSIONS: Structured feedback following a single adolescent and mother SP encounter resulted in significant improvement in the adolescent-specific communication skills of PGY1s in performing an adolescent interview.

Uncovering the unknown: A grounded theory study exploring the impact of self-awareness on the culture of feedback in residency education.

AIM: Self-assessment and reflection are essential for meaningful feedback. We aimed to explore whether the well-known Johari window model of self-awareness could guide feedback conversations between faculty and residents and enhance the institutional feedback culture. METHODS: We had previously explored perceptions of residents and faculty regarding sociocultural factors impacting feedback. We re-analyzed data targeting themes related to self-assessment, reflection, feedback seeking and acceptance, aiming to generate individual and institutional feedback strategies applicable to each quadrant of the window. RESULTS: We identified the following themes for each quadrant: (1) Behaviors known to self and others - Validating the known; (2) Behaviors unknown to self but known to others - Accepting the blind; (3) Behaviors known to self and unknown to others - Disclosure of hidden; and (4) Behaviors unknown to self and others - Uncovering the unknown. Normalizing self-disclosure of limitations, encouraging feedback seeking, training in nonjudgmental feedback and providing opportunities for longitudinal relationships could promote self-awareness, ultimately expanding the "open" quadrant of the Johari window. CONCLUSIONS: The Johari window, a model of self-awareness in interpersonal communications, could provide a robust framework for individuals to improve their feedback conversations and institutions to design feedback initiatives that enhance its quality and impact.

A Constructive Reframing of Student Roles and Systems Learning in Medical Education Using a Communities of Practice Lens.

Health systems are in the midst of a transformation that is being driven by a variety of forces. This has important implications for medical educators because clinical practice environments play a key role in learning and professional development, and evolving health systems are beginning to demand that providers have "systems-ready" knowledge, attitudes, and skills. Such implications provide a clear mandate for medical schools to modify their goals and prepare physicians to practice flexibly within teams and effectively contribute to the improvement of health care delivery. In this context, the concepts of value-added medical education, authentic student roles, and health systems science are emerging as increasingly important. In this Article, the authors use a lens informed by communities of practice theory to explore these three concepts, examining the implications that the communities of practice theory has in the constructive reframing of educational practices-particularly common student roles and experiences-and charting future directions for medical education that better align with the needs of the health care system. The authors apply several key features of the communities of practice theory to current experiential roles for students, then propose a new approach to students' clinical experiences-value-added clinical systems learning roles-that provides students with opportunities to make meaningful contributions to patient care while learning health systems science at the patient and population level. Finally, the authors discuss implications for professional role formation and anticipated challenges to the design and implementation of value-added clinical systems learning roles.

R2C2 in Action: Testing an Evidence-Based Model to Facilitate Feedback and Coaching in Residency.

BACKGROUND: Feedback is increasingly seen as a collaborative conversation between supervisors and learners, where learners are actively and reflectively engaged with feedback and use it to improve. Based on this, and through earlier research, we developed an evidence- and theory-informed, 4-phase model for facilitating feedback and practice improvement-the R2C2 model (relationship, reaction, content, coaching). OBJECTIVE: Our goal was to explore the utility and acceptability of the R2C2 model in residency education, specifically for engaging residents in their feedback and in using it to improve, as well as the factors influencing its use. METHODS: This qualitative study used the principles of design research. We recruited residents and their supervisors in 2 programs, internal medicine and pediatrics. We prepared supervisors to use the R2C2 model during their regular midrotation and/or end-of-rotation feedback sessions with participating residents to discuss their progress and assessment reports. We conducted debriefing interviews with supervisors and residents after each session. We analyzed transcripts as a team using template and content analysis. RESULTS: Of 61 residents, 7 residents (11%) participated with their supervisors (n = 5). Schedules and sensitivity to feedback prevented broader enrollment. Supervisors found the structured R2C2 format useful. Residents and supervisors reported that the coaching phase was novel and helpful, and that the R2C2 model engaged both groups in collaborative, reflective, goal-oriented feedback discussions. CONCLUSIONS: Participants found that using the R2C2 model enabled meaningful feedback conversations, identification of goals for improvement, and development of strategies to meet those goals.

Multimodality Technologies in the Assessment of Hematolymphoid Neoplasms.

Accurate assessment of tissues for hematolymphoid neoplasms requires an integrated multiparameter approach. Although morphologic examination by light microscopy remains the mainstay of initial assessment for hematolymphoid neoplasms, immunophenotypic analysis by immunohistochemistry and/or flow cytometry is essential to determine the pattern of differentiation and to detect minimal disease when morphology is inconclusive. In some cases, immunophenotypic analysis provides additional information for targeted immunotherapy and prognostication. Genotypic studies, including cytogenetics, fluorescence in situ hybridization, DNA microarray, polymerase chain reaction, and/or next-generation sequencing, are also imperative for subclassification of the genetically defined disease entities in the current World Health Organization classification of hematolymphoid neoplasms. Moreover, genotypic studies can establish clonality, stratify patients to determine appropriate treatment, and monitor patients for treatment response.

The invisible work of distributed medical education: exploring the contributions of audiovisual professionals, administrative professionals and faculty teachers.

Distributed medical education (DME) is becoming increasingly prevalent. Much of the published literature on DME has focused on the experiences of learners in distributed programs; however, our empirical work leads us to believe that DME changes the context significantly, not only for learners, but also for other important members of the educational community including audiovisual professionals, administrative professionals and faculty teachers. Based on a three-year ethnographic study, we provide a detailed account of how alliances between various workers involved in DME develop to produce and deliver an undergraduate medical curriculum across geographically separate campuses. We explore the question 'What is the work involved in the delivery of a DME program?' and cast a critical gaze on the essential but invisible, and therefore potentially unrecognized and underappreciated, contributions of AV professionals, administrative professionals, and faculty teachers. Our goal is to make visible the complexity of DME, including the essential contributions of these workers. The study was theoretically framed in sociomateriality and conceptually framed in Star and Strauss' notion of articulation work.