Development of core entrustable professional activities linked to a competency-based veterinary education framework

Purpose: Despite the adoption of competency-based education in some veterinary schools over the past 15 years, only recently has a concerted effort been directed toward this in veterinary education internationally. Methods: In 2015, educational leaders from the Association of American Veterinary Medical Colleges (AAVMC) member schools came together with a strong call to action to create shared tools for clinical competency assessment. Results: This resulted in the formation of the AAVMC Competency-Based Veterinary Education (CBVE) Working Group, which then embarked on the creation of a shared competency framework and the development of eight core entrustable professional activities (EPAs) linked to this framework. Conclusions: This paper will report on the development of these EPAs and their integration with the concurrently-developed CBVE Framework

Cis and trans regulatory mechanisms control AP2-mediated B cell receptor endocytosis via select tyrosine-based motifs.

Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding YxxØ motifs, including four that are present within two immunoreceptor tyrosine-based activation motifs (ITAMs). Using a combination of in vitro and in situ approaches, we establish that the sole mediator of AP2-dependent BCR internalization is the membrane proximal ITAM YxxØ motif in CD79b, which is a major target of mutation in ABC DLBCL. In addition, we establish that BCR internalization can be regulated at a minimum of two different levels: regulation of YxxØ AP2 binding in cis by downstream ITAM-embedded DCSM and QTAT regulatory elements and regulation in trans by the partner cytoplasmic domain of the CD79 heterodimer. Beyond establishing the basic rules governing BCR internalization, these results illustrate an underappreciated role for ITAM residues in controlling clathrin-dependent endocytosis and highlight the complex mechanisms that control the activity of AP2 binding motifs in this receptor system

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Cyclic estrus-like behaviour associated with an excessive sex-hormone production from an adrenocortical carcinoma in a cat

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α−hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery

Collaborative Development of Core Entrustable Professional Activities for Veterinary Education

Entrustable professional activities (EPAs) have been proposed as a practical framework for the implementation of competency-based education. As veterinary education moves toward a competency-based approach, core EPAs provide a context for assessment of workplace activities. This article reports on the development of eight core clinical EPAs for veterinary education created through multi-institutional collaboration, with international input from veterinary educators and veterinary educational leaders. These core EPAs are intended as minimal expectations for clinical activities that should be assessed for every graduate of Association of American Veterinary Medical Colleges member institutions. Adoption of the core EPAs and the associated Competency-Based Veterinary Education (CBVE) framework by veterinary schools is intended to promote Day One graduate competence and thereby enhance patient care and client service

Collaborative Development of a Shared Framework for Competency-Based Veterinary Education

Competency-based medical education is an educational innovation implemented in health professions worldwide as a means to ensure graduates meet patient and societal needs. The focus on student-centered education and programmatic outcomes offers a series of benefits to learners, institutions and society. However, efforts to establish a shared, comprehensive competency-based framework in veterinary education have lagged. This article reports on the development and outcome of a competency-based veterinary education (CBVE) framework created through multi-institutional collaboration with international input from veterinary educators and veterinary educational leaders. The CBVE Framework is designed to reflect the competencies expected of new graduates from member institutions of the Association of American Veterinary Medical Colleges (AAVMC). The CBVE Framework consists of nine domains of competence and 32 competencies, each supplemented with illustrative sub-competencies to guide veterinary schools in implementing competency-based education in their local context. The nine domains of competence are: clinical reasoning and decision-making; individual animal care and management; animal population care and management; public health; communication; collaboration; professionalism and professional identity; financial and practice management; and scholarship. Developed through diverse input to facilitate broad adoption, the CBVE Framework provides the foundation for competency-based curricula and outcomes assessment in veterinary education internationally. We believe that other groups seeking to design a collective product for broad adoption might find useful the methods used to develop the CBVE Framework, including establishing expertise diversity within a small-to-medium size working group, soliciting progressive input and feedback from stakeholders, and engaging in consensus building and critical reflection throughout the development process