Using 3D-bioprinted models to study pediatric neural crest-derived tumors.

The use of three-dimensional (3D) bioprinting has remained at the forefront of tissue engineering and has recently been employed for generating bioprinted solid tumors to be used as cancer models to test therapeutics. In pediatrics, neural crest-derived tumors are the most common type of extracranial solid tumors. There are only a few tumor-specific therapies that directly target these tumors, and the lack of new therapies remains detrimental to improving the outcomes for these patients. The absence of more efficacious therapies for pediatric solid tumors, in general, may be due to the inability of the currently employed preclinical models to recapitulate the solid tumor phenotype. In this study, we utilized 3D bioprinting to generate neural crest-derived solid tumors. The bioprinted tumors consisted of cells from established cell lines and patient-derived xenograft tumors mixed with a 6% gelatin/1% sodium alginate bioink. The viability and morphology of the bioprints were analyzed via bioluminescence and immunohisto chemistry, respectively. We compared the bioprints to traditional twodimensional (2D) cell culture under conditions such as hypoxia and therapeutics. We successfully produced viable neural crest-derived tumors that retained the histology and immunostaining characteristics of the original parent tumors. The bioprinted tumors propagated in culture and grew in orthotopic murine models. Furthermore, compared to cells grown in traditional 2D culture, the bioprinted tumors were resistant to hypoxia and chemotherapeutics, suggesting that the bioprints exhibited a phenotype that is consistent with that seen clinically in solid tumors, thus potentially making this model superior to traditional 2D culture for preclinical investigations. Future applications of this technology entail the potential to rapidly print pediatric solid tumors for use in high-throughput drug studies, expediting the identification of novel, individualized therapies.

"PLEASE Complete Your Evaluations!" Strategies to Engage Faculty in Competency-Based Assessments.

Competency-based assessments (CBAs) have gained traction in graduate medical education and inform important learner outcomes through the continuum of medical training. Active participation in new CBAs presents challenges to faculty working in a busy clinical environment. As such, the implementation of new CBAs can be approached with intention to foster acceptance and engagement with new evaluations. This paper describes strategies utilized to implement CBAs among clinician educators during a national assessment pilot. Our methods are grounded in educational, psychological, business, ecological, communication, and information technology theory. Our primary interventions included creating a multilevel vision, engaging a dedicated work group, incorporating quality improvement methodology, and integrating technology to successfully implement the assessments. These practical and effective interventions may also be applied to the implementation of other educational innovations.

A cell-penetrating MARCKS mimetic selectively triggers cytolytic death in glioblastoma.

Glioblastoma (GBM) is an aggressive malignancy with limited effectiveness of standard of care therapies including surgery, radiation, and temozolomide chemotherapy necessitating novel therapeutics. Unfortunately, GBMs also harbor several signaling alterations that protect them from traditional therapies that rely on apoptotic programmed cell death. Because almost all GBM tumors have dysregulated phosphoinositide signaling as part of that process, we hypothesized that peptide mimetics derived from the phospholipid binding domain of Myristoylated alanine-rich C-kinase substrate (MARCKS) could serve as a novel GBM therapeutic. Using molecularly classified patient-derived xenograft (PDX) lines, cultured in stem-cell conditions, we demonstrate that cell permeable MARCKS effector domain (ED) peptides potently target all GBM molecular classes while sparing normal human astrocytes. Cell death mechanistic testing revealed that these peptides produce rapid cytotoxicity in GBM that overcomes caspase inhibition. Moreover, we identify a GBM-selective cytolytic death mechanism involving plasma membrane targeting and intracellular calcium accumulation. Despite limited relative partitioning to the brain, tail-vein peptide injection revealed tumor targeting in intracranially implanted GBM PDX. These results indicate that MARCKS ED peptide therapeutics may overcome traditional GBM resistance mechanisms, supporting further development of similar agents.

The Emergence and Spread of Practice-Based Medical Education Research Networks.

Educational research networks leverage shared goals and common infrastructure to overcome traditional barriers to medical education research, including small sample sizes, lack of generalizability, need for expertise in statistical analysis, and limitations on data sharing. The diversity of extant network models today is exciting and provides a set of common options and challenges that newly emerging networks can expect. These include decisions about network focus, organization of data, sampling strategies, funding, and governance. Common challenges include managing authorship, human subjects protection rules, data use agreements, and statistical disclosure control. Medical education research networks both advance the field and develop the researchers who participate in them. The authors repeat the call that they and others have made for the development of networks to promulgate best practices and coordinate multinetwork (multinational, multispecialty, and cross-curriculum) studies.

Reported Pediatrics Milestones (Mostly) Measure Program, Not Learner Performance.

PURPOSE: Semiannually, U.S. pediatrics residency programs report resident milestone levels to the Accreditation Council for Graduate Medical Education (ACGME). The Pediatrics Milestones Assessment Collaborative (PMAC, consisting of the National Board of Medical Examiners, American Board of Pediatrics, and Association of Pediatric Program Directors) developed workplace-based assessments of 2 inferences: readiness to serve as an intern with a supervisor present (D1) and readiness to care for patients with a supervisor nearby in the pediatric inpatient setting (D2). The authors compared learner and program variance in PMAC scores with ACGME milestones. METHOD: The authors examined sources of variance in PMAC scores and milestones between November 2015 and May 2017 of 181 interns at 8 U.S. pediatrics residency programs using random effects models with program, competency, learner, and program × competency components. RESULTS: Program-related milestone variance was substantial (54% D1, 68% D2), both in comparison to learner milestone variance (22% D1, 14% D2) and program variance in the PMAC scores (12% D1, 10% D2). In contrast, learner variance represented 44% (D1) or 26% (D2) of variance in PMAC scores. Within programs, PMAC scores were positively correlated with milestones for all but one competency. CONCLUSIONS: PMAC assessments provided scores with little program-specific variance and were more sensitive to differences in learners within programs compared with milestones. Milestones reflected greater differences by program than by learner. This may represent program-based differences in intern performance or in use of milestones as a reporting scale. Comparing individual learner milestones without adjusting for programs is problematic.

ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor.

The treatment of lymphatic anomaly, a rare devastating disease spectrum of mostly unknown etiologies, depends on the patient manifestations1. Identifying the causal genes will allow for developing affordable therapies in keeping with precision medicine implementation2. Here we identified a recurrent gain-of-function ARAF mutation (c.640T>C:p.S214P) in a 12-year-old boy with advanced anomalous lymphatic disease unresponsive to conventional sirolimus therapy and in another, unrelated, adult patient. The mutation led to loss of a conserved phosphorylation site. Cells transduced with ARAF-S214P showed elevated ERK1/2 activity, enhanced lymphangiogenic capacity, and disassembly of actin skeleton and VE-cadherin junctions, which were rescued using the MEK inhibitor trametinib. The functional relevance of the mutation was also validated by recreating a lymphatic phenotype in a zebrafish model, with rescue of the anomalous phenotype using a MEK inhibitor. Subsequent therapy of the lead proband with a MEK inhibitor led to dramatic clinical improvement, with remodeling of the patient's lymphatic system with resolution of the lymphatic edema, marked improvement in his pulmonary function tests, cessation of supplemental oxygen requirements and near normalization of daily activities. Our results provide a representative demonstration of how knowledge of genetic classification and mechanistic understanding guides biologically based medical treatments, which in our instance was life-saving.

Myristoylated alanine-rich C-kinase substrate effector domain phosphorylation regulates the growth and radiation sensitization of glioblastoma.

Glioblastoma harbors frequent alterations in receptor tyrosine kinases, phosphatidylinositol­3 kinase (PI3K) and phosphatase and tensin homolog (PTEN) that dysregulate phospholipid signaling driven tumor proliferation and therapeutic resistance. Myristoylated alanine­rich C­kinase substrate (MARCKS) is a 32 kDa intrinsically unstructured protein containing a polybasic (+13) effector domain (ED), which regulates its electrostatic sequestration of phospholipid phosphatidylinositol (4,5)­bisphosphate (PIP2), and its binding to phosphatidylserine, calcium/calmodulin, filamentous actin, while also serving as a nuclear localization sequence. MARCKS ED is phosphorylated by protein kinase C (PKC) and Rho­associated protein kinase (ROCK) kinases; however, the impact of MARCKS on glioblastoma growth and radiation sensitivity remains undetermined. In the present study, using a tetracycline­inducible system in PTEN­null U87 cells, we demonstrate that MARCKS overexpression suppresses growth and enhances radiation sensitivity in vivo. A new image cytometer, Xcyto10, was utilized to quantify differences in MARCKS ED phosphorylation on localization and its association with filamentous actin. The overexpression of the non­phosphorylatable ED mutant exerted growth­suppressive and radiation­sensitizing effects, while the pseudo­phosphorylated ED mutant exhibited an enhanced colony formation and clonogenic survival ability. The identification of MARCKS protein­protein interactions using co­immunoprecipitation coupled with tandem mass spectrometry revealed novel MARCKS­associated proteins, including importin­ß and ku70. On the whole, the findings of this study suggest that the determination of the MARCKS ED phosphorylation status is essential to understanding the impact of MARCKS on cancer progression.

Does Incorporating a Measure of Clinical Workload Improve Workplace-Based Assessment Scores? Insights for Measurement Precision and Longitudinal Score Growth From Ten Pediatrics Residency Programs.

PURPOSE: This study investigates the impact of incorporating observer-reported workload into workplace-based assessment (WBA) scores on (1) psychometric characteristics of WBA scores and (2) measuring changes in performance over time using workload-unadjusted versus workload-adjusted scores. METHOD: Structured clinical observations and multisource feedback instruments were used to collect WBA data from first-year pediatrics residents at 10 residency programs between July 2016 and June 2017. Observers completed items in 8 subcompetencies associated with Pediatrics Milestones. Faculty and resident observers assessed workload using a sliding scale ranging from low to high; all item scores were rescaled to a 1-5 scale to facilitate analysis and interpretation. Workload-adjusted WBA scores were calculated at the item level using three different approaches, and aggregated for analysis at the competency level. Mixed-effects regression models were used to estimate variance components. Longitudinal growth curve analyses examined patterns of developmental score change over time. RESULTS: On average, participating residents (n = 252) were assessed 5.32 times (standard deviation = 3.79) by different raters during the data collection period. Adjusting for workload yielded better discrimination of learner performance, and higher reliability, reducing measurement error by 28%. Projections in reliability indicated needing up to twice the number of raters when workload-unadjusted scores were used. Longitudinal analysis showed an increase in scores over time, with significant interaction between workload and time; workload also increased significantly over time. CONCLUSIONS: Incorporating a measure of observer-reported workload could improve the measurement properties and the ability to interpret WBA scores.

Pathogenic variant in EPHB4 results in central conducting lymphatic anomaly.

Central conducting lymphatic anomaly (CCLA) is one of the complex lymphatic anomalies characterized by dilated lymphatic channels, lymphatic channel dysmotility and distal obstruction affecting lymphatic drainage. We performed whole exome sequencing (WES) of DNA from a four-generation pedigree and examined the consequences of the variant by transfection of mammalian cells and morpholino and rescue studies in zebrafish. WES revealed a heterozygous mutation in EPHB4 (RefSeq NM_004444.4; c.2334 + 1G>C) and RNA-Seq demonstrated that the EPHB4 mutation destroys the normal donor site, which leads to the use of a cryptic splice donor that results in retention of the intervening 12-bp intron sequence. Transient co-expression of the wild-type and mutant EPHB4 proteins showed reduced phosphorylation of tyrosine, consistent with a loss-of-function effect. Zebrafish ephb4a morpholino resulted in vessel misbranching and deformities in the lymphatic vessel development, indicative of possible differentiation defects in lymphatic vessels, mimicking the lymphatic presentations of the patients. Immunoblot analysis using zebrafish lysates demonstrated over-activation of mTORC1 as a consequence of reduced EPHB4 signaling. Strikingly, drugs that inhibit mTOR signaling or RAS-MAPK signaling effectively rescued the misbranching phenotype in a comparable manner. Moreover, knock-in of EPHB4 mutation in HEK293T cells also induced mTORC1 activity. Our data demonstrate the pathogenicity of the identified EPHB4 mutation as a novel cause of CCLA and suggesting that ERK inhibitors may have therapeutic benefits in such patients with complex lymphatic anomalies.

A novel workplace-based assessment for competency-based decisions and learner feedback.

BACKGROUND: Increased recognition of the importance of competency-based education and assessment has led to the need for practical and reliable methods to assess relevant skills in the workplace. METHODS: A novel milestone-based workplace assessment system was implemented in 15 pediatrics residency programs. The system provided: (1) web-based multisource feedback (MSF) and structured clinical observation (SCO) instruments that could be completed on any computer or mobile device; and (2) monthly feedback reports that included competency-level scores and recommendations for improvement. RESULTS: For the final instruments, an average of five MSF and 3.7 SCO assessment instruments were completed for each of 292 interns; instruments required an average of 4-8 min to complete. Generalizability coefficients >0.80 were attainable with six MSF observations. Users indicated that the new system added value to their existing assessment program; the need to complete the local assessments in addition to the new assessments was identified as a burden of the overall process. CONCLUSIONS: Outcomes - including high participation rates and high reliability compared to what has traditionally been found with workplace-based assessment - provide evidence for the validity of scores resulting from this novel competency-based assessment system. The development of this assessment model is generalizable to other specialties.

Conducting Quantitative Medical Education Research: From Design to Dissemination.

Rigorous medical education research is critical to effectively develop and evaluate the training we provide our learners. Yet many clinical medical educators lack the training and skills needed to conduct high-quality medical education research. We offer guidance on conducting sound quantitative medical education research. Our aim is to equip readers with the key skills and strategies necessary to conduct successful research projects, highlighting new concepts and controversies in the field. We utilize Glassick's criteria for scholarship as a framework to discuss strategies to ensure that the research question of interest is worthy of further study and how to use existing literature and conceptual frameworks to strengthen a research study. Through discussions of the strengths and limitations of commonly used study designs, we expose the reader to particular nuances of these decisions in medical education research and discuss outcomes generally focused on, as well as strategies for determining the significance of consequent findings. We conclude with information on critiquing research findings and preparing results for dissemination to a broad audience. Practical planning worksheets and comprehensive tables illustrating key concepts are provided in order to guide researchers through each step of the process. Medical education research provides wonderful opportunities to improve how we teach our learners, to satisfy our own intellectual curiosity, and ultimately to enhance the care provided to patients.

Validity Evidence From Ratings of Pediatric Interns and Subinterns on a Subset of Pediatric Milestones.

PURPOSE: To investigate evidence for validity of faculty members' pediatric milestone (PM) ratings of interns (first-year residents) and subinterns (fourth-year medical students) on nine subcompetencies related to readiness to serve as a pediatric intern in the inpatient setting. METHOD: The Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network (APPD LEARN) and the National Board of Medical Examiners collaborated to investigate the utility of assessments of the PMs for trainees' performance. Data from 32 subinterns and 179 interns at 17 programs were collected from July 2012 through April 2013. Observers used several tools to assess learners. At each site, a faculty member used these data to make judgments about the learner's current developmental milestone in each subcompetency. Linear mixed models were fitted to milestone judgments to examine their relationship with learner's rank and subcompetency. RESULTS: On a 5-point developmental scale, mean milestone levels for interns ranged from 3.20 (for the subcompetency Work effectively as a member of a team) to 3.72 (Humanism) and for subinterns from 2.89 (Organize and prioritize care) to 3.61 (Professionalization). Mean milestone ratings were significantly higher for the Professionalism competency (3.59-3.72) for all trainees compared with Patient Care (2.89-3.24) and Personal and Professional Development (3.33-3.51). Mean intern ratings were significantly higher than mean subintern ratings for all nine subcompetencies except Professionalization, Humanism, and Trustworthiness. CONCLUSIONS: The PMs had a coherent internal structure and could distinguish between differing levels of trainees, which supports their validation for documenting developmental progression of pediatric trainees.

MARCKS phosphorylation is modulated by a peptide mimetic of MARCKS effector domain leading to increased radiation sensitivity in lung cancer cell lines.

Lung cancer is the leading cause of cancer-associated mortality in the United States. Kinase hyperactivation is a known mechanism of tumorigenesis. The phosphorylation status of the plasma membrane-associated protein myristoylated alanine rich C-kinase substrate (MARCKS) effector domain (ED) was previously established as being important in the sensitivity of lung cancer to radiation. Specifically, when MARCKS ED was in a non-phosphorylated state, lung cancer cells were more susceptible to ionizing radiation and experienced prolonged double-strand DNA breaks. Additional studies demonstrated that the phosphorylation status of MARCKS ED is important for gene expression and in vivo tumor growth. The present study used a peptide mimetic of MARCKS ED as a therapeutic intervention to modulate MARCKS phosphorylation. Culturing A549, H1792 and H1975 lung cancer cell lines with the MARCKS ED peptide led to reduced levels of phosphorylated MARCKS and phosphorylated Akt serine/threonine kinase 1. Further investigation demonstrated that the peptide therapy was able to reduce lung cancer cell proliferation and increase radiation sensitivity. In addition, the MARCKS peptide therapy was able to prolong double-strand DNA breaks following ionizing radiation exposure. The results of the present study demonstrate that a peptide mimetic of MARCKS ED is able to modulate MARCKS phosphorylation, leading to an increase in sensitivity to radiation.

The Pediatrics Milestones Assessment Pilot: Development of Workplace-Based Assessment Content, Instruments, and Processes.

PURPOSE: To report on the development of content and user feedback regarding the assessment process and utility of the workplace-based assessment instruments of the Pediatrics Milestones Assessment Pilot (PMAP). METHOD: One multisource feedback instrument and two structured clinical observation instruments were developed and refined by experts in pediatrics and assessment to provide evidence for nine competencies based on the Pediatrics Milestones (PMs) and chosen to inform residency program faculty decisions about learners' readiness to serve as pediatric interns in the inpatient setting. During the 2012-2013 PMAP study, 18 U.S. pediatric residency programs enrolled interns and subinterns. Faculty, residents, nurses, and other observers used the instruments to assess learner performance through direct observation during a one-month rotation. At the end of the rotation, data were aggregated for each learner, milestone levels were assigned using a milestone classification form, and feedback was provided to learners. Learners and site leads were surveyed and/or interviewed about their experience as participants. RESULTS: Across the sites, 2,338 instruments assessing 239 learners were completed by 630 unique observers. Regarding end-of-rotation feedback, 93% of learners (128/137) agreed the assessments and feedback "helped me understand how those with whom I work perceive my performance," and 85% (117/137) agreed they were "useful for constructing future goals or identifying a developmental path." Site leads identified several benefits and challenges to the assessment process. CONCLUSIONS: PM-based instruments used in workplace-based assessment provide a meaningful and acceptable approach to collecting evidence of learner competency development. Learners valued feedback provided by PM-based assessment.

Medical education practice-based research networks: Facilitating collaborative research.

BACKGROUND: Research networks formalize and institutionalize multi-site collaborations by establishing an infrastructure that enables network members to participate in research, propose new studies, and exploit study data to move the field forward. Although practice-based clinical research networks are now widespread, medical education research networks are rapidly emerging. AIMS: In this article, we offer a definition of the medical education practice-based research network, a brief description of networks in existence in July 2014 and their features, and a more detailed case study of the emergence and early growth of one such network, the Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network (APPD LEARN). METHODS: We searched for extant networks through peer-reviewed literature and the world-wide web. RESULTS: We identified 15 research networks in medical education founded since 2002 with membership ranging from 8 to 120 programs. Most focus on graduate medical education in primary care or emergency medicine specialties. CONCLUSIONS: We offer four recommendations for the further development and spread of medical education research networks: increasing faculty development, obtaining central resources, studying networks themselves, and developing networks of networks.

The Effector Domain of MARCKS Is a Nuclear Localization Signal that Regulates Cellular PIP2 Levels and Nuclear PIP2 Localization.

Translocation to the nucleus of diacylglycerol kinase (DGK)- ζ is dependent on a sequence homologous to the effector domain of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS). These data would suggest that MARCKS could also localize to the nucleus. A single report demonstrated immunofluorescence staining of MARCKS in the nucleus; however, further experimental evidence confirming the specific domain responsible for this localization has not been reported. Here, we report that MARCKS is present in the nucleus in GBM cell lines. We then over-expressed wild-type MARCKS (WT) and MARCKS with the effector domain deleted (ΔED), both tagged with V5-epitope in a GBM cell line with low endogenous MARCKS expression (U87). We found that MARCKS-WT localized to the nucleus, while the MARCKS construct without the effector domain remained in the cytoplasm. We also found that over-expression of MARCKS-WT resulted in a significant increase in total cellular phosphatidyl-inositol (4,5) bisphosphate (PIP2) levels, consistent with prior evidence that MARCKS can regulate PIP2 levels. We also found increased staining for PIP2 in the nucleus with MARCKS-WT over-expression compared to MARCKS ΔED by immunofluorescence. Interestingly, we observed MARCKS and PIP2 co-localization in the nucleus. Lastly, we found changes in gene expression when MARCKS was not present in the nucleus (MARCKS ΔED). These data indicate that the MARCKS effector domain can function as a nuclear localization signal and that this sequence is critical for the ability of MARCKS to regulate PIP2 levels, nuclear localization, and gene expression. These data suggests a novel role for MARCKS in regulating nuclear functions such as gene expression.

Targeting the effector domain of the myristoylated alanine rich C-kinase substrate enhances lung cancer radiation sensitivity.

Lung cancer is the leading cause of cancer related deaths. Common molecular drivers of lung cancer are mutations in receptor tyrosine kinases (RTKs) leading to activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pro-growth, pro-survival signaling pathways. Myristoylated alanine rich C-kinase substrate (MARCKS) is a protein that has the ability to mitigate this signaling cascade by sequestering the target of PI3K, phosphatidylinositol (4,5)-bisphosphate (PIP2). As such, MARCKS has been implicated as a tumor suppressor, though there is some evidence that MARCKS may be tumor promoting in certain cancer types. Since the MARCKS function depends on its phosphorylation status, which impacts its subcellular location, MARCKS role in cancer may depend highly on the signaling context. Currently, the importance of MARCKS in lung cancer biology is limited. Thus, we investigated MARCKS in both clinical specimens and cell culture models. Immunohistochemistry scoring of MARCKS protein expression in a diverse lung tumor tissue array revealed that the majority of squamous cell carcinomas stained positive for MARCKS while other histologies, such as adenocarcinomas, had lower levels. To study the importance of MARCKS in lung cancer biology, we used inducible overexpression of wild-type (WT) and non-phosphorylatable (NP)-MARCKS in A549 lung cancer cells that had a low level of endogenous MARCKS. We found that NP-MARCKS expression, but not WT-MARCKS, enhanced the radiosensitivity of A549 cells in part by inhibiting DNA repair as evidenced by prolonged radiation-induced DNA double strand breaks. We confirmed the importance of MARCKS phosphorylation status by treating several lung cancer cell lines with a peptide mimetic of the phosphorylation domain, the effector domain (ED), which effectively attenuated cell growth as measured by cell index. Thus, the MARCKS ED appears to be an important target for lung cancer therapeutic development.

An online evidence based medicine exercise prompts reflection in third year medical students.

BACKGROUND: Reflective practice is a desirable trait in physicians, yet there is little information about how it is taught to or learned by medical students. The purpose of this study was to determine whether an online Evidence Based Medicine (EBM) exercise with a face-to-face debriefing session would prompt third year medical students to reflect on their current skills and lead them to further reflection on clinical decision making in the future. METHODS: All third year medical students at the University Of Maryland School Of Medicine who completed their pediatrics clerkship between 7/1/09 and 2/11/11 were required to complete the EBM exercise. Following completion each student received a personal report (Learning Profile) of their responses and attended a one hour large group debriefing session. Student responses to a survey following the debriefing sessions were analyzed using a post-test survey design with a single experimental cohort. RESULTS: Ninety-five percent of students completing the debriefing survey indicated that the debriefing session helped them better understand their learning profiles; 68% stated that their profiles allowed them to evaluate themselves and their decisions. Sixty-three percent noted that participating in the exercise and the debrief would lead them to either learn more about EBM and use EBM more in the future or reflect more on their own decision making. CONCLUSIONS: The EBM exercise was a successful way to introduce the concept of reflective practice to third year medical students, and the graphic Learning Profiles were effective instigators of discussion and reflection.

Front-line ordering clinicians: matching workforce to workload.

BACKGROUND: Matching workforce to workload is particularly important in healthcare delivery, where an excess of workload for the available workforce may negatively impact processes and outcomes of patient care and resident learning. Hospitals currently lack a means to measure and match dynamic workload and workforce factors. OBJECTIVES: This article describes our work to develop and obtain consensus for use of an objective tool to dynamically match the front-line ordering clinician (FLOC) workforce to clinical workload in a variety of inpatient settings. METHODS: We undertook development of a tool to represent hospital workload and workforce based on literature reviews, discussions with clinical leadership, and repeated validation sessions. We met with physicians and nurses from every clinical care area of our large, urban children's hospital at least twice. RESULTS: We successfully created a tool in a matrix format that is objective and flexible and can be applied to a variety of settings. We presented the tool in 14 hospital divisions and received widespread acceptance among physician, nursing, and administrative leadership. The hospital uses the tool to identify gaps in FLOC coverage and guide staffing decisions. DISCUSSION: Hospitals can better match workload to workforce if they can define and measure these elements. The Care Model Matrix is a flexible, objective tool that quantifies the multidimensional aspects of workload and workforce. The tool, which uses multiple variables that are easily modifiable, can be adapted to a variety of settings.