Does Attending a Regional Medical Campus Influence the Training Outcomes of Family Medicine Residents?

Introduction: Indiana University School of Medicine (IUSM) is the largest medical school in the nation, with its main campus located in Indianapolis and eight regional medical campuses (RMC) distributed across the state. In this study, we compared the survey responses of family medicine residents who had attended medical school at the main campus in Indianapolis versus an RMC to see if there were any noticeable differences in their residency training outcomes. Methods: From 2012 to 2017, in the spring of each year, a cross-sectional survey was administered to all final-year family medicine residents graduating from the eleven family medicine residency programs in Indiana. A total of 519 out of 520 residents completed the survey. Of whom, 132 respondents indicated they had graduated from IUSM; 45 reported they had attended the Indianapolis campus and 87 had attended one of the RMCs in the state. Our dataset for this study was comprised of these 132 respondents. Chi-square test or Fisher’s exact test were used to compare responses between groups. P-values ≤ 0.05 were considered statistically significant. Results: In the ACGME competency areas, the residents who attended an RMC versus the Indianapolis campus were significantly more likely to report being fully competent in Medical Knowledge (90% vs. 76%, p = 0.032) and Systems-Based Practice (83% vs. 64%, p = 0.019). Additionally, the residents who attended an RMC compared to their Indianapolis counterparts reported significantly higher rates of being trained to serve rural populations (73% vs. 52%, p = 0.017) as well as being fully competent to serve rural populations (69% vs. 42%, p = 0.003). However, the residents who attended an RMC were no more likely to establish a practice in a rural area than were the residents who attended Indianapolis (18% vs. 17%, p = 0.845). Conclusions: Based on these self-reported data, the family medicine residents who attended an RMC may perceive themselves to be better-prepared in a few core competency areas, as well as in serving rural populations, compared to those who attended the Indianapolis campus. These findings suggest that IUSM’s complex statewide system of medical education may offer some unique advantages in preparing students for residency, especially in family medicine

Tracking Medical Students and Graduates from Hometown to Practice using Geographic Information Systems, 2011-2017

Background: Indiana University School of Medicine (IUSM) through its statewide system provides medical education and clinical experiences across Indiana for more than 1,450 medical students in nine regions, including Indianapolis and eight regional medical campuses (RMCs). The majority of medical students begin their education distributed among the RMCs, and some students continue clinical experiences at the RMCs for their third and fourth years. Methods: We used a Geographic Information System (GIS) to visualize and document the contribution of our RMCs in Indiana to the physician workforce pipeline. Using data from the 2011-2017 graduating classes, we created a geospatial database that linked key information from student records and public domain sources (e.g., hometown, campus assignment, PGY1 specialty, and practice) with their corresponding locational information. ArcGIS 10.5 GIS software was used to produce a series of maps to visualize patterns in student outcomes among the RMCs over time. Results: By using GIS to track medical trainees from hometown to practice, we can provide accurate visualization of extensive geographic data. The maps revealed similarities and differences among the RMCs not fully appreciated until visually mapped, including the specialty choice of students from different campuses and the proportion of graduates practicing in medically underserved areas of the state. Conclusions: GIS maps and their analyses can identify strengths and distinctions among the RMCs while providing accurate descriptions of the role of geography in the professional development journey of the physician workforce. This ongoing project is a major step toward integrating GIS as a familiar tool in academic administration and health workforce research to assist future decision-making by the school leadership

Lens connexins α3Cx46 and α8Cx50 interact with zonula occludens protein-1 (ZO-1)

Connexin α1Cx43 has previously been shown to bind to the PDZ domain–containing protein ZO-1. The similarity of the carboxyl termini of this connexin and the lens fiber connexins α3Cx46 and α8Cx50 suggested that these connexins may also interact with ZO-1. ZO-1 was shown to be highly expressed in mouse lenses. Colocalization of ZO-1 with α3Cx46 and α8Cx50 connexins in fiber cells was demonstrated by immunofluorescence and by fracture-labeling electron microscopy but showed regional variations throughout the lens. ZO-1 was found to coimmunoprecipitate with α3Cx46 and α8Cx50, and pull-down experiments showed that the second PDZ domain of ZO-1 was involved in this interaction. Transiently expressed α3Cx46 and α8Cx50 connexins lacking the COOH-terminal residues did not bind to the second PDZ domain but still formed structures resembling gap junctions by immunofluorescence. These results indicate that ZO-1 interacts with lens fiber connexins α3Cx46 and α8Cx50 in a manner similar to that previously described for α1Cx43. The spatial variation in the interaction of ZO-1 with lens gap junctions is intriguing and is suggestive of multiple dynamic roles for this association

Understanding the Current Anatomical Competence Landscape: Comparing Perceptions of Program Directors, Residents, and Fourth Year Medical Students

A mixed methods survey of fourth year medical students, resident physicians, and residency program directors at the Indiana University School of Medicine gathered perceptions of anatomical competence—defined as the anatomical education necessary for effective clinical practice. The survey items explored numerous aspects of anatomical competence, including the most effective modes of instruction, perceptions of readiness for clinical practice, and specific suggestions for improving anatomical education during medical school and residency. The response rate was 46% for fourth year medical students, 47% for residents (as graduates from 137 medical schools), and 71% for program directors. A majority of students and residents reported the following: that their course in Gross Anatomy prepared them well for clinical practice; that cadaveric dissection was important in the early development of their anatomical competence; and that placing a greater emphasis on clinical relevance in medical school would have improved their anatomical competence even further. However, in terms of anatomical preparedness upon entering residency, the program directors rated their residents less prepared than the residents rated themselves. All three groups agreed there is need for additional opportunities for anatomical educational during medical school and residency. Suggestions for improving anatomical education included: provide more opportunities for cadaveric dissection during medical school and residency; more consistent teaching of anatomy for clinical practice; more workshops that review anatomy; and better integration of anatomy with the teaching of other subjects during medical school

Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma

Despite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% +/- 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% +/- 2% vs. 57.4% +/- 1.8% (p < 0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% +/- 1.5% in lithium treated cells vs. 56.6 +/- 3% (p < 0.01)) accompanied by increased number of.H2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% +/- 8% for lithium treated cells vs. 27% +/- 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.B.R.A.I.N Child Canada; Cancer Research UK; Brain Tumour Charity; Hungarian Brain Research Program [KTIA_13_NAP-A-V/3]; Janos Bolyai Scholarship of the Hungarian Academy of Sciences [TAMOP-4.2.2. A-11/1/KONV-2012-0025]; German Cancer Aid/Dr. Mildred Scheel Foundation for Cancer Research; Cure Childhood Cancer Foundation; St. Baldrick's Foundation; Southeastern Brain Tumor Foundation; Action Medical Research; [CZ.1.05/2.1.00/03.0101]; [CZ.1.07/2.3.00/20.0183

A meta-analysis of the investment-uncertainty relationship

In this article we use meta-analysis to investigate the investment-uncertainty relationship. We focus on the direction and statistical significance of empirical estimates. Specifically, we estimate an ordered probit model and transform the estimated coefficients into marginal effects to reflect the changes in the probability of finding a significantly negative estimate, an insignificant estimate, or a significantly positive estimate. Exploratory data analysis shows that there is little empirical evidence for a positive relationship. The regression results suggest that the source of uncertainty, the level of data aggregation, the underlying model specification, and differences between short- and long-run effects are important sources of variation in study outcomes. These findings are, by and large, robust to the introduction of a trend variable to capture publication trends in the literature. The probability of finding a significantly negative relationship is higher in more recently published studies. JEL Classification: D21, D80, E22 1

A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor

© 2019 Elsevier Inc. Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death. Sin-Chan et al. uncover a C19MC-LIN28A-MYCN super-enhancer-dependent oncogenic circuit in embryonal tumors with multilayered rosettes (ETMRs). The circuit entraps an early neural lineage network to sustain embryonic epigenetic programming and is vulnerable to bromodomain inhibition, which promotes ETMR cell death

Finding needles in haystacks:Linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Reannotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.The Intramural Research Programs of the National Center for Biotechnology Information, National Library of Medicine and the National Human Genome Research Institute, both at the National Institutes of Health.http://www.ncbi.nlm.nih.gov/bioproject/PRJNA177353am201