Imprinting on Clinical Rotations: Multisite Survey of High- and Low-Value Medical Student Behaviors and Relationship with Healthcare Intensity.

BACKGROUND: Physician behaviors are important to high-value care, and the learning environment medical students encounter on clinical clerkships may imprint their developing practice patterns. OBJECTIVES: To explore potential imprinting on clinical rotations by (a) describing high- and low-value behaviors among medical students and (b) examining relationships with regional healthcare intensity (HCI). DESIGN: Multisite cross-sectional survey PARTICIPANTS: Third- and fourth-year students at nine US medical schools MAIN MEASURES: Survey items measured high-value (n = 10) and low-value (n = 9) student behaviors. Regional HCI was measured using Dartmouth Atlas End-of-Life Chronic Illness Care data (ratio of physician visits per decedent compared with the US average, hospital care intensity index, ratio of medical specialty to primary care physician visits per decedent). Associations between regional HCI and student behaviors were examined using unadjusted and adjusted (controlling for age, sex, and year in school) logistic regression analyses, using median item ratings to summarize reported engagement in high- and low-value behaviors. KEY RESULTS: Of 2623 students invited, 1304 (50%) responded. Many reported trying to determine healthcare costs (1085/1234, 88%), but only 45% (571/1257) reported including cost details in case presentations. Students acknowledged suggesting tests solely to anticipate what their supervisor would want (1143/1220, 94%), show off their ability to generate a broad differential diagnosis (1072/1218, 88%), satisfy curiosity (958/1217, 79%), protect the team from liability (938/1215, 77%), and build clinical experience (533/1217, 44%). Students in higher intensity regions reported significantly more low-value behaviors: each one-unit increase in the ratio of physician visits per decedent increased the odds of reporting low-value behaviors by 20% (OR 1.20, 95% CI 1.04-1.38; P = 0.01). CONCLUSIONS: Third- and fourth-year medical students report engaging in both high- and low-value behaviors, which are related to regional HCI. This underscores the importance of the clinical learning environment and suggests imprinting is already underway during medical school.

Attitudes toward cost-conscious care among U.S. physicians and medical students: analysis of national cross-sectional survey data by age and stage of training.

BACKGROUND: The success of initiatives intended to increase the value of health care depends, in part, on the degree to which cost-conscious care is endorsed by current and future physicians. This study aimed to first analyze attitudes of U.S. physicians by age and then compare the attitudes of physicians and medical students. METHODS: A paper survey was mailed in mid-2012 to 3897 practicing physicians randomly selected from the American Medical Association Masterfile. An electronic survey was sent in early 2015 to all 5,992 students at 10 U.S. medical schools. Survey items measured attitudes toward cost-conscious care and perceived responsibility for reducing healthcare costs. Physician responses were first compared across age groups (30-40 years, 41-50 years, 51-60 years, and > 60 years) and then compared to student responses using Chi square tests and logistic regression analyses (controlling for sex). RESULTS: A total of 2,556 physicians (65%) and 3395 students (57%) responded. Physician attitudes generally did not differ by age, but differed significantly from those of students. Specifically, students were more likely than physicians to agree that cost to society should be important in treatment decisions (p < 0.001) and that physicians should sometimes deny beneficial but costly services (p < 0.001). Students were less likely to agree that it is unfair to ask physicians to be cost-conscious while prioritizing patient welfare (p < 0.001). Compared to physicians, students assigned more responsibility for reducing healthcare costs to hospitals and health systems (p < 0.001) and less responsibility to lawyers (p < 0.001) and patients (p < 0.001). Nearly all significant differences persisted after controlling for sex and when only the youngest physicians were compared to students. CONCLUSIONS: Physician attitudes toward cost-conscious care are similar across age groups. However, physician attitudes differ significantly from medical students, even among the youngest physicians most proximate to students in age. Medical student responses suggest they are more accepting of cost-conscious care than physicians and attribute more responsibility for reducing costs to organizations and systems rather than individuals. This may be due to the combined effects of generational differences, new medical school curricula, students' relative inexperience providing cost-conscious care within complex healthcare systems, and the rapidly evolving U.S. healthcare system.

Competency milestones for medical students: Design, implementation, and analysis at one medical school.

Competency-based assessment seeks to align measures of performance directly with desired learning outcomes based upon the needs of patients and the healthcare system. Recognizing that assessment methods profoundly influence student motivation and effort, it is critical to measure all desired aspects of performance throughout an individual's medical training. The Accreditation Council for Graduate Medical Education (ACGME) defined domains of competency for residency; the subsequent Milestones Project seeks to describe each learner's progress toward competence within each domain. Because the various clinical disciplines defined unique competencies and milestones within each domain, it is difficult for undergraduate medical education to adopt existing GME milestones language. This paper outlines the process undertaken by one medical school to design, implement and improve competency milestones for medical students. A team of assessment experts developed milestones for a set of focus competencies; these have now been monitored in medical students over two years. A unique digital dashboard enables individual, aggregate and longitudinal views of student progress by domain. Validation and continuous quality improvement cycles are based upon expert review, user feedback, and analysis of variation between students and between assessors. Experience to date indicates that milestone-based assessment has significant potential to guide the development of medical students.

Changing Medical School IT to Support Medical Education Transformation.

PROBLEM: Many medical schools are modifying curricula to reflect the rapidly evolving health care environment, but schools struggle to provide the educational informatics technology (IT) support to make the necessary changes. Often a medical school's IT support for the education mission derives from isolated work units employing separate technologies that are not interoperable. INTERVENTION: We launched a redesigned, tightly integrated, and novel IT infrastructure to support a completely revamped curriculum at the Vanderbilt School of Medicine. This system uses coordinated and interoperable technologies to support new instructional methods, capture students' effort, and manage feedback, allowing the monitoring of students' progress toward specific competency goals across settings and programs. CONTEXT: The new undergraduate medical education program at Vanderbilt, entitled Curriculum 2.0, is a competency-based curriculum in which the ultimate goal is medical student advancement based on performance outcomes and personal goals rather than a time-based sequence of courses. IT support was essential in the creation of Curriculum 2.0. In addition to typical learning and curriculum management functions, IT was needed to capture data in the learning workflow for analysis, as well as for informing individual and programmatic success. We aligned people, processes, and technology to provide the IT infrastructure for the organizational transformation. OUTCOMES: Educational IT personnel were successfully realigned to create the new IT system. The IT infrastructure enabled monitoring of student performance within each competency domain across settings and time via personal student electronic portfolios. Students use aggregated performance data, derived in real time from the portfolio, for mentor-guided performance assessment, and for creation of individual learning goals and plans. Poorly performing students were identified earlier through online communication systems that alert the appropriate instructor or coach of low quiz grades or missed learning goals. Graphical and narrative displays of a student's competency performance across courses and clinical experiences informed high-stake decisions made about student progress by the promotions committee. Similarly, graphical display of aggregate student outcomes provided education leaders with information needed to adjust and improve the curriculum. LESSONS LEARNED: With the alignment of people, processes, and technology, educational IT can facilitate transformational steps in the training of medical students.

Reducing the time from initial call to first appointment: the impact of patient access redesign and a nurse navigation program.

Fox Chase Cancer Center (FCCC) participated in the NCCN Opportunities for Improvement project with the purpose of optimizing the quality of care delivered at FCCC to patients with breast cancer based on the ASCO and NCCN Guidelines. Historically, FCCC's performance has demonstrated a high level of concordance, based on findings from the NCCN Oncology Outcomes Database project benchmarking data in breast cancer. Access to the NCCN Breast Cancer Timing in Continuation and Transition of Care (TiCToC) Measures data analysis (performed by NCCN) provided an opportunity to further identify specific opportunities related to care along the continuum. The initial goal of the project was to continue participation in the NCCN Oncology Outcomes Database for Breast Cancer, with the overall objective of sustaining high concordance. FCCC's recent data were compared with historical data and benchmarked against those from other participating NCCN Member Institutions.

Evaluating the Role of Competency-Based Behavioral Interviewing in Holistic Medical School Admissions.

PROBLEM: Holistic review is a multifaceted concept that aims to increase diversity and applicant fit with program needs by complementing traditional academic requirements with appraisal of a wider range of personal characteristics and experiences. Behavioral interviewing has been practiced and studied in human resources, business, and organizational psychology for over 50 years. Its premise is that future performance can be anticipated from past actions. However, many of the interview approaches within the holistic framework are resource intensive and logistically challenging. APPROACH: The Vanderbilt University School of Medicine instituted a competency-based behavioral interview (CBBI) to augment the selection process in 2012. Behavioral interviews are based on key competencies needed for entering students and require applicants to reflect on their actual experiences and what they learned from them. The authors reviewed 5 years of experience (2015-2019) to evaluate how CBBI scores contributed to the overall assessment of applicants for admission. OUTCOMES: The final admission committee decision for each applicant was determined by reviewing multiple factors, with no single assessment determining the final score. The CBBI and summary interview scores showed a strong association (P < .005), suggesting that the summary interviewer, who had access to the full applicant file, and the CBBI interviewer, who did not, assessed similar strengths despite the 2 different approaches, or that the strengths assessed tracked in the same direction. Students whose 2 interview scores were not aligned were less likely to be accepted to the school. NEXT STEPS: The review raised awareness about the cultural aspects of interpreting the competencies and the need to expand our cultural framework throughout interviewer training. Findings indicate that CBBIs have the potential to reduce bias related to over-reliance on standardized metrics; however, additional innovation and research are needed.

Structural characterization of a unique interface between carbohydrate response element-binding protein (ChREBP) and 14-3-3ß protein.

Carbohydrate response element-binding protein (ChREBP) is an insulin-independent, glucose-responsive transcription factor that is expressed at high levels in liver hepatocytes where it plays a critical role in converting excess carbohydrates to fat for storage. In response to fluctuating glucose levels, hepatic ChREBP activity is regulated in large part by nucleocytoplasmic shuttling of ChREBP protein via interactions with 14-3-3 proteins. The N-terminal ChREBP regulatory region is necessary and sufficient for glucose-responsive ChREBP nuclear import and export. Here, we report the crystal structure of a complex of 14-3-3ß bound to the N-terminal regulatory region of ChREBP at 2.4 Å resolution. The crystal structure revealed that the α2 helix of ChREBP (residues 117-137) adopts a well defined α-helical conformation and binds 14-3-3 in a phosphorylation-independent manner that is different from all previously characterized 14-3-3 and target protein-binding modes. ChREBP α2 interacts with 14-3-3 through both electrostatic and van der Waals interactions, and the binding is partially mediated by a free sulfate or phosphate. Structure-based mutagenesis and binding assays indicated that disrupting the observed 14-3-3 and ChREBP α2 interface resulted in a loss of complex formation, thus validating the novel protein interaction mode in the 14-3-3ß·ChREBP α2 complex.

Competing Discourses about Youth Sexual Exploitation in Canadian News Media.

Media holds the power to create, maintain, or break down stigmatizing attitudes, which affect policies, funding, and services. To understand how Canadian news media depicts the commercial sexual exploitation of children and youth, we examined 835 Canadian newspaper articles from 1989-2008 using a mixed methods critical discourse analysis approach, comparing representations to existing research about sexually exploited youth. Despite research evidence that equal rates of boys and girls experience exploitation, Canadian news media depicted exploited youth predominantly as heterosexual girls, and described them alternately as victims or workers in a trade, often both in the same story. News media mentioned exploiters far less often than victims, and portrayed them almost exclusively as male, most often called 'customers' or 'consumers,' and occasionally 'predators'; in contrast, research has documented the majority of sexually exploited boys report female exploiters. Few news stories over the past two decades portrayed the diversity of victims, perpetrators, and venues of exploitation reported in research. The focus on victims but not exploiters helps perpetuate stereotypes of sexual exploitation as business or a 'victimless crime,' maintains the status quo, and blurs responsibility for protecting youth under the UN Convention on the Rights of the Child. Health care providers and researchers can be advocates for accuracy in media coverage about sexual exploitation; news reporters and editors should focus on exploiters more than victims, draw on existing research evidence to avoid perpetuating stereotypes, and use accurate terms, such as commercial sexual exploitation, rather than terms related to business or trade.

Competencies for the Use of Artificial Intelligence-Based Tools by Health Care Professionals.

PURPOSE: The expanded use of clinical tools that incorporate artificial intelligence (AI) methods has generated calls for specific competencies for effective and ethical use. This qualitative study used expert interviews to define AI-related clinical competencies for health care professionals. METHOD: In 2021, a multidisciplinary team interviewed 15 experts in the use of AI-based tools in health care settings about the clinical competencies health care professionals need to work effectively with such tools. Transcripts of the semistructured interviews were coded and thematically analyzed. Draft competency statements were developed and provided to the experts for feedback. The competencies were finalized using a consensus process across the research team. RESULTS: Six competency domain statements and 25 subcompetencies were formulated from the thematic analysis. The competency domain statements are: (1) basic knowledge of AI: explain what AI is and describe its health care applications; (2) social and ethical implications of AI: explain how social, economic, and political systems influence AI-based tools and how these relationships impact justice, equity, and ethics; (3) AI-enhanced clinical encounters: carry out AI-enhanced clinical encounters that integrate diverse sources of information in creating patient-centered care plans; (4) evidence-based evaluation of AI-based tools: evaluate the quality, accuracy, safety, contextual appropriateness, and biases of AI-based tools and their underlying data sets in providing care to patients and populations; (5) workflow analysis for AI-based tools: analyze and adapt to changes in teams, roles, responsibilities, and workflows resulting from implementation of AI-based tools; and (6) practice-based learning and improvement regarding AI-based tools: participate in continuing professional development and practice-based improvement activities related to use of AI tools in health care. CONCLUSIONS: The 6 clinical competencies identified can be used to guide future teaching and learning programs to maximize the potential benefits of AI-based tools and diminish potential harms.

Clinical use of artificial intelligence requires AI-capable organizations.

Artificial intelligence-based algorithms are being widely implemented in health care, even as evidence is emerging of bias in their design, problems with implementation, and potential harm to patients. To achieve the promise of using of AI-based tools to improve health, healthcare organizations will need to be AI-capable, with internal and external systems functioning in tandem to ensure the safe, ethical, and effective use of AI-based tools. Ideas are starting to emerge about the organizational routines, competencies, resources, and infrastructures that will be required for safe and effective deployment of AI in health care, but there has been little empirical research. Infrastructures that provide legal and regulatory guidance for managers, clinician competencies for the safe and effective use of AI-based tools, and learner-centric resources such as clear AI documentation and local health ecosystem impact reviews can help drive continuous improvement.

Importin-alpha protein binding to a nuclear localization signal of carbohydrate response element-binding protein (ChREBP).

Carbohydrate response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in the glucose-mediated induction of genes involved in hepatic glycolysis and lipogenesis. Circulating blood glucose levels affect ChREBP activity in hepatocytes largely by post-translational mechanisms that include phosphorylation-dependent subcellular localization. Previously, we showed that ChREBP is retained in the cytosol by phosphorylation-dependent binding to 14-3-3 protein dimers and identified the α2 helix (residues 125-135) phospho-Ser(140) domain as the primary 14-3-3 binding site (Sakiyama, H., Wynn, R. M., Lee, W. R., Fukasawa, M., Mizuguchi, H., Gardner, K. H., Repa, J. J., and Uyeda, K. (2008) J. Biol. Chem. 283, 24899-24908). To enter the nucleus in response to high glucose, ChREBP must bind importin-α; this heterodimer then forms a complex with importin-ß to interact with the nuclear pore complex. In this work, we recharacterized the importin-α binding nuclear localization signal (NLS) of rat ChREBP, identifying it as an extended classical bipartite NLS encompassing minimally residues 158-190. Replacing Lys(159)/Lys(190) residues of ChREBP with alanine resulted in loss of importin-α binding, glucose-stimulated transcriptional activity and nuclear localization. A secondary 14-3-3 protein binding site also was identified, the α3 helix (residues 170-190) phospho-Ser(196) domain. Importin-α and 14-3-3 were found to bind competitively to this secondary site. These results suggest an important mechanism by which importin-α and 14-3-3 control movement of ChREBP in and out of the nucleus in response to changes in glucose levels in liver and thus further suggest that the extended NLS of ChREBP is a critical glucose-sensing, glucose-responsive site.

Considering Clinician Competencies for the Implementation of Artificial Intelligence-Based Tools in Health Care: Findings From a Scoping Review.

BACKGROUND: The use of artificial intelligence (AI)-based tools in the care of individual patients and patient populations is rapidly expanding. OBJECTIVE: The aim of this paper is to systematically identify research on provider competencies needed for the use of AI in clinical settings. METHODS: A scoping review was conducted to identify articles published between January 1, 2009, and May 1, 2020, from MEDLINE, CINAHL, and the Cochrane Library databases, using search queries for terms related to health care professionals (eg, medical, nursing, and pharmacy) and their professional development in all phases of clinical education, AI-based tools in all settings of clinical practice, and professional education domains of competencies and performance. Limits were provided for English language, studies on humans with abstracts, and settings in the United States. RESULTS: The searches identified 3476 records, of which 4 met the inclusion criteria. These studies described the use of AI in clinical practice and measured at least one aspect of clinician competence. While many studies measured the performance of the AI-based tool, only 4 measured clinician performance in terms of the knowledge, skills, or attitudes needed to understand and effectively use the new tools being tested. These 4 articles primarily focused on the ability of AI to enhance patient care and clinical decision-making by improving information flow and display, specifically for physicians. CONCLUSIONS: While many research studies were identified that investigate the potential effectiveness of using AI technologies in health care, very few address specific competencies that are needed by clinicians to use them effectively. This highlights a critical gap.

Effect of Smartphone App-Based Education on Clinician Prescribing Habits in a Learning Health Care System: A Randomized Cluster Crossover Trial.

Importance: Effective methods for engaging clinicians in continuing education for learning-based practice improvement remain unknown. Objective: To determine whether a smartphone-based app using spaced education with retrieval practice is an effective method to increase evidence-based practice. Design, Setting, and Participants: A prospective, unblinded, single-center, crossover randomized clinical trial was conducted at a single academic medical center from January 6 to April 24, 2020. Vanderbilt University Medical Center clinicians prescribing intravenous fluids were invited to participate in this study. Interventions: All clinicians received two 4-week education modules: 1 on prescribing intravenous fluids and 1 on prescribing opioid and nonopioid medications (counterbalancing measure), over a 12-week period. The order of delivery was randomized 1:1 such that 1 group received the fluid management module first, followed by the pain management module after a 4-week break, and the other group received the pain management module first, followed by the fluid management module after a 4-week break. Main Outcomes and Measures: The primary outcome was evidence-based clinician prescribing behavior concerning intravenous fluids in the inpatient setting and pain medication prescribing on discharge from the hospital. Results: A total of 354 participants were enrolled and randomized, with 177 in group 1 (fluid then pain management education) and 177 in group 2 (pain management then fluid education). During the overall study period, 16 868 questions were sent to 349 learners, with 11 783 (70.0%) being opened: 10 885 (92.4%) of those opened were answered and 7175 (65.9%) of those answered were answered correctly. The differences between groups changed significantly over time, indicated by the significant interaction between educational intervention and time (P = .002). Briefly, at baseline evidence-concordant IV fluid ordered 7.2% less frequently in group 1 than group 2 (95% CI, -19.2% to 4.9%). This was reversed after training at 4% higher (95% CI, -8.2% to 16.0%) in group 1 than group 2, a more than doubling in the odds of evidence-concordant ordering (OR, 2.56, 95% CI, 0.80-8.21). Postintervention, all gains had been reversed with less frequent ordering in group 1 than group 2 (-9.5%, 95% CI, -21.6% to 2.7%). There was no measurable change in opioid prescribing behaviors at any time point. Conclusions and Relevance: In this randomized clinical trial, use of smartphone app learning modules resulted in statistically significant short-term improvement in some prescribing behaviors. However, this effect was not sustained over the long-term. Additional research is needed to understand how to sustain improvements in care delivery as a result of continuous professional development at the institutional level. Trial Registration: ClinicalTrials.gov Identifier: NCT03771482.

Quiz-Based Microlearning at Scale: a Rapid Educational Response to COVID-19.

Virtual quizzing is a viable model for continuing education at a large scale, particularly during the COVID-19 pandemic. By leveraging technology, microlearning encourages mobile education that is engaging, flexible, and accessible. Learners reported that this format was effective and preferable to traditional methods of education, suggesting further opportunity for innovation.

Comparison of Two Learning Modalities on Continuing Medical Education Consumption and Knowledge Acquisition: A Pilot Randomized Controlled Trial.

BACKGROUND: Research has demonstrated that active learning, spaced education, and retrieval-based practice can improve knowledge acquisition, knowledge retention, and clinical practice. Furthermore, learners prefer active learning modalities that use the testing effect and spaced education as compared to passive, lecture-based education. However, most research has been performed with students and residents rather than practicing physicians. To date, most continuing medical education (CME) opportunities use passive learning models, such as face-to-face meetings with lecture-style didactic sessions. The aim of this study was to investigate learner engagement, as measured by the number of CME credits earned, via two different learning modalities. METHODS: Diplomates of the American Board of Anesthesiology or candidates for certification through the board (referred to colloquially and for the remainder of this article as board certified or board eligible) were provided an opportunity to enroll in the study. Participants were recruited via email. Once enrolled, they were randomized into 1 of 2 groups: web-app-based CME (Webapp CME) or an online interface that replicated online CME (Online CME). The intervention period lasted 6 weeks and participants were provided educational content using one of the two approaches. As an incentive for participation, CME credits could be earned (without cost) during the intervention period and for completion of the postintervention quiz. The same number of CME credits was available to each group. RESULTS: Fifty-four participants enrolled and completed the study. The mean number of CME credits earned was greater in the Webapp group compared to the Online group (12.3 ± 1.4 h versus 4.5 ± 2.3 h, P < .001). Concerning knowledge acquisition, the difference in postintervention quiz scores was not statistically significant (Webapp 70% ± 7% versus Online 60% ± 11%, P = .11). However, only 29% of the Online group completed the postintervention quiz, versus 77% of the Webapp group (P < .001), possibly showing a greater rate of learner engagement in the Webapp group. CONCLUSION: In this prospective, randomized controlled pilot study, we demonstrated that daily spaced education delivered to learners through a smartphone web app resulted in greater learner engagement than an online modality. Further research with larger trials is needed to confirm our findings.

Embedding Learning in a Learning Health Care System to Improve Clinical Practice.

PROBLEM: In an ideal learning health care system (LHS), clinicians learn from what they do and do what they learn, closing the evidence-to-practice gap. In operationalizing an LHS, great strides have been made in knowledge generation. Yet, considerable challenges remain to the broad uptake of identified best practices. To bridge the gap from generating actionable knowledge to applying that knowledge in clinical practice, and ultimately to improving outcomes, new information must be disseminated to and implemented by frontline clinicians. To date, the dissemination of this knowledge through traditional avenues has not achieved meaningful practice change quickly. APPROACH: Vanderbilt University Medical Center (VUMC) developed QuizTime, a smartphone application learning platform, to provide a mechanism for embedding workplace-based clinician learning in the LHS. QuizTime leverages spaced education and retrieval-based practice to facilitate practice change. Beginning in January 2020, clinician-researchers and educators at VUMC designed a randomized, controlled trial to test whether the QuizTime learning system influenced clinician behavior in the context of recent evidence supporting the use of balanced crystalloids rather than saline for intravenous fluid management and new regulations around opioid prescribing. OUTCOMES: Whether spaced education and retrieval-based practice influence clinician behavior and patient outcomes at the VUMC system level will be tested using the data currently being collected. NEXT STEPS: These findings will inform future directions for developing and deploying learning approaches at scale in an LHS, with the goal of closing the evidence-to-practice gap.

Granzyme C supports efficient CTL-mediated killing late in primary alloimmune responses.

It is well established that granzymes A and B play a role in CTL killing of target cells by the perforin-dependent granule exocytosis pathway. The functions of multiple additional granzymes expressed in CTL are less well defined. In the present studies, CTL generated from mice deficient in dipeptidyl peptidase 1 (DPP1) were used to investigate the contribution of granzyme C to CTL killing of allogeneic target cells. DPP1 is required for activation of granzymes A and B by proteolytic removal of their N-terminal dipeptide prodomains while a significant portion of granzyme C is processed normally in the absence of DPP1. Cytotoxicity of DPP1(-/-) CTL generated in early (5-day) MLC in vitro and in peritoneal exudate cells 5 days after initial allogeneic sensitization in vivo was significantly impaired compared with wild-type CTL. Following 3 days of restimulation with fresh allogeneic stimulators however, cytotoxicity of these DPP1(-/-) effector cells was comparable to that of wild-type CTL. Killing mediated by DPP1(-/-) CTL following restimulation was rapid, perforin dependent, Fas independent and associated with early mitochondrial injury, phosphatidyl serine externalization, and DNA degradation, implicating a granzyme-dependent apoptotic pathway. The increased cytotoxicity of DPP1(-/-) CTL following restimulation coincided with increased expression of granzyme C. Moreover, small interfering RNA inhibition of granzyme C expression during restimulation significantly decreased cytotoxicity of DPP1(-/-) but not wild-type CTL. These results indicate that during late primary alloimmune responses, granzyme C can support CTL-mediated killing by the granule exocytosis pathway in the absence of functional granzymes A or B.

Age of Sexual Consent Law in Canada: Population-Based Evidence for Law and Policy.

This study evaluated the implications of the 2008 increase in age for sexual consent in Canada using a population health survey of Canadian adolescents. Government rationales for the increase asserted younger adolescents were more likely to experience sexual exploitation and engage in risky sexual behaviour than adolescents 16 and older. Using data from sexually experienced adolescents in the 2008 British Columbia Adolescent Health Survey (BC AHS, N=6,262; age range 12 - 19; 52% female), analyses documented the scope of first intercourse partners who were not within the 'close in age' exemptions, then compared sexual behaviours of younger teens (14 and 15 years) with older teens (16 and 17) navigating their first year of sexual activity. Comparisons included: forced sex, sex under the influence of alcohol or drugs, multiple partners, condom use, effective contraception use, self-reported sexually transmitted infections, and pregnancy involvement. Results showed very few 14- and 15-year-olds had first intercourse partners who were not within the 'close in age' exemptions based on age (boys: <2%, girls: 3-5%). In contrast, among 12- and 13-year-olds (a group unaffected by the law's change) between 25% and 50% had first intercourse partners who were not within the 'close in age' exemptions, and almost 40% of teens who first had sex before age 12 reported a first partner age 20 years or more. In their first year of intercourse, 14- and 15-year-olds were slightly more likely to report forced sex and 3 or more partners than older teens, but otherwise made similarly healthy decisions. This study demonstrates the feasibility of evaluating policy using population health data and shows that better strategies are needed to protect children 13 and under from sexual abuse.

The Vanderbilt Program in Interprofessional Learning: Sustaining a Longitudinal, Clinical Experience That Aligns Practice With Education.

PROBLEM: Designing and sustaining a longitudinal, clinic-based interprofessional learning experience is logistically challenging, which has limited the educational opportunities available in health professions schools. The authors discuss the Vanderbilt Program in Interprofessional Learning (VPIL), which addresses some of the challenges facing clinic-based interprofessional experiences. APPROACH: VPIL places first- and second-year students from 4 professional degree programs (medicine, nursing, pharmacy, social work) in Nashville, Tennessee, on teams where they work and learn together in authentic clinical environments over a 2-year period. The program was implemented in 2010 and includes 3 components: a summer immersion experience, seminar-based classroom and simulation sessions, and a weekly clinical experience. Students also complete a capstone quality improvement project. VPIL administrators have set up structures at the institutional, clinic, faculty, and student levels that have contributed to the sustainability of the program. OUTCOMES: Between 2010 and 2019, VPIL admitted 398 students who participated on 91 clinical teams. In addition, 55 clinical preceptors and 12 core faculty trained students for future collaborative practice. The program has received consistently high ratings from students, who have produced 69 quality improvement projects at their clinics. These projects have addressed aspects of the care delivery process and produced durable materials, showing that the program has contributed to important innovations in the health system. NEXT STEPS: VPIL faculty continue to improve the curriculum and administrative structures and work to expand the program to reach a wider variety of health professions students. Going forward, lessons from the program could assist educators in creating opportunities for students to learn interprofessionally and deliver high value health care in increasingly complex delivery systems.

Characterization of ionotrophic purinergic receptors in hepatocytes.

UNLABELLED: Ionotrophic purinergic (P2X) receptors function as receptor-gated cation channels, where agonist binding leads to opening of a nonselective cation pore permeable to both Na(+) and Ca(2+). Based on evidence that extracellular adenosine 5'-triphosphate (ATP) stimulates glucose release from liver, these studies evaluate whether P2X receptors are expressed by hepatocytes and contribute to ATP-dependent calcium signaling and glucose release. Studies were performed in isolated hepatocytes from rats and mice and hepatoma cells from humans and rats. Transcripts and protein for both P2X4 and P2X7 were detectable, and immunohistochemistry of intact liver revealed P2X4 in the basolateral and canalicular domains. In whole cell patch clamp studies, exposure to the P2X4/P2X7 receptor agonist 2'3'-O-(4-benzoyl-benzoyl)-adenosine 5'-triphosphate (BzATP; 10 microM) caused a rapid increase in membrane Na(+) conductance. Similarly, with Fluo-3 fluorescence, BzATP induced an increase in intracellular [Ca(2+)]. P2X4 receptors are likely involved because the calcium response to BzATP was inhibited by Cu(2+), and the P2X4 modulators Zn(2+) and ivermectin (0.3-3 microM) each increased intracellular [Ca(2+)]. Exposure to BzATP decreased cellular glycogen content; and P2X4 receptor messenger RNA increased in glycogen-rich liver samples. CONCLUSION: These studies provide evidence that P2X4 receptors are functionally important in hepatocyte Na(+) and Ca(2+) transport, are regulated by extracellular ATP and divalent cation concentrations, and may constitute a mechanism for autocrine regulation of hepatic glycogen metabolism.