A genome-wide association study on medulloblastoma.

INTRODUCTION: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. METHODS: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. RESULTS: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10-5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10-8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10-4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10-3). CONCLUSION: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

Do-It-Yourself Business Intelligence for the Radiologist-Lessons Learned From 10-Year Trends in an Abdominal Imaging Division at a Tertiary Medical Center.

"Big data" has changed the way businesses operate in finance, insurance, communications, manufacturing, and logistics, with companies reporting successful outcomes from the implementation of data-driven analytics. Health care has slowly started leveraging big data analysis to identify more cost-efficient and effective care for patients. Business intelligence software aims to help with this transition, converting large data sets into useful, actionable information. Radiology practices have used business intelligence toolkits in the past to increase reading room productivity, scanner efficiency, and patient throughput. Although these tactics have driven down costs and increased volumes, an essential aspect of radiology practice growth-consumer satisfaction-remains largely unexplored. The first commandment of marketing is "know thy customer," which is the key to increasing radiology's value to referring clinicians who use our services. Our article explores the business case behind a basic business intelligence model, giving any radiologist the instruments to access and draw business conclusions from their radiology information system data.

Should Radiology Residency Interviews Remain Virtual? Results of a Multi-institutional Survey Inform the Debate.

RATIONALE AND OBJECTIVES: The recent completion of the inaugural virtual interview season has triggered calls for the permanency of virtual interviews in the radiology resident selection process. We designed a study to assess the inaugural 2020-2021 virtual interview season and inform the anticipated debate on the future of radiology residency interviews. MATERIALS AND METHODS: Forty-four and 39-question survey instruments developed for program directors (PDs) and applicants, respectively, were distributed through the Radiology Residency Education Research Alliance to measure the demographics, experiences with technology, attitudes toward the virtual interview season and attitudes about proposed changes to the interview process. Comparisons were made between demographics and survey queries. RESULTS: PD and applicant response rates were 74% (25/34) and 45% (84/186), respectively. Eighty percent (20/25) of PDs and 76% (64/84) of applicants described the virtual interview season as excellent or very good. Sixty percent of PDs agreed or strongly agreed with the statement "The benefits of the virtual interview season outweighed the drawbacks," while 24% disagreed or strongly disagreed, and 16% were neutral. Among applicants, 80% agreed or strongly agreed, 10% disagreed or strongly disagreed, and 10% were neutral toward the same statement. Ninety-two percent of PDs noted that their rank order list performed the same or better than in years prior. Both PDs and applicants identified applicant equity and wellness as major benefits of virtual interviews, while identifying over-application and interview hoarding as significant detriments. CONCLUSION: The virtual interview provides an adequate substitute for the conventional in-person residency interview, with real and perceived benefits to applicant wellness, equity, and financial well-being. The downsides of virtual interviews, namely over-application and interview hoarding, have workable solutions.

From Beginning to End: A Single Radiology Residency Program's Experience with Web-Based Resident Recruitment during COVID-19 and a Review of the Literature.

COVID-19 disrupted the practice of in-person visits for the 2020-2021 recruitment cycle. This past year, Graduate Medical Education (GME) programs converted to online interviews and virtual visits for all applicants. Given the unpredictable nature of this pandemic, it remains unclear when or if conventional travel for residency interviews will resume. Therefore, it is important to reflect on this past season and look ahead to our next recruitment and interview cycle. Here, we review prior publications studying faculty and applicant experiences with web-based interviewing strategies, and we describe our own residency program's recruitment strategy for a virtual interview season, including survey results of reactions by both interviewers and candidates following our first season in this new era of virtual meetings and interviews. Web-based recruitment and interviews are feasible and can be done well with careful planning and preparation of those involved. Concerns persist primarily among applicants that virtual visits to a training program are inadequate for providing sufficient information prior to ranking. Regardless of future travel restrictions, GME programs will likely benefit all stakeholders by offering web-based recruitment and interviews, while also providing opportunities for optional in-person visits.

Accuracy of Preoperative Breast MRI Versus Conventional Imaging in Measuring Pathologic Extent of Invasive Lobular Carcinoma.

OBJECTIVE: To determine whether invasive lobular carcinoma (ILC) extent is more accurately depicted with preoperative MRI (pMRI) than conventional imaging (mammography and/or ultrasound). METHODS: After IRB approval, we retrospectively identified women with pMRIs (February 2005 to January 2014) to evaluate pure ILC excluding those with ipsilateral pMRI BI-RADS 4 or 5 findings or who had neoadjuvant chemotherapy. Agreement between imaging and pathology sizes was summarized using Bland-Altman plots, absolute and percent differences, and the intraclass correlation coefficient (ICC). Rates of underestimation and overestimation were evaluated and their associations with clinical features were explored. RESULTS: Among the 56 women included, pMRI demonstrated better agreement with pathology than conventional imaging by mean absolute difference (1.6 mm versus -7.8 mm, P < 0.001), percent difference (10.3% versus -16.4%, P < 0.001), and ICC (0.88 versus 0.61, P = 0.019). Conventional imaging more frequently underestimated ILC span than pMRI using a 5 mm difference threshold (24/56 (43%) versus 10/56 (18%), P < 0.001), a 25% threshold (19/53 (36%) versus 10/53 (19%), P = 0.035), and T category change (17/56 (30%) versus 7/56 (13%), P = 0.006). Imaging-pathology size concordance was greater for MRI-described solitary masses than other lesions for both MRI and conventional imaging (P < 0.05). Variability of conventional imaging was lower for patients ≥ the median age of 62 years than for younger patients (SD: 12 mm versus 22 mm, P = 0.012). CONCLUSION: MRI depicts pure ILC more accurately than conventional imaging and may have particular value for younger women.

The level of origin firing inversely affects the rate of replication fork progression.

DNA damage slows DNA synthesis at replication forks; however, the mechanisms remain unclear. Cdc7 kinase is required for replication origin activation, is a target of the intra-S checkpoint, and is implicated in the response to replication fork stress. Remarkably, we found that replication forks proceed more rapidly in cells lacking Cdc7 function than in wild-type cells. We traced this effect to reduced origin firing, which results in fewer replication forks and a consequent decrease in Rad53 checkpoint signaling. Depletion of Orc1, which acts in origin firing differently than Cdc7, had similar effects as Cdc7 depletion, consistent with decreased origin firing being the source of these defects. In contrast, mec1-100 cells, which initiate excess origins and also are deficient in checkpoint activation, showed slower fork progression, suggesting the number of active forks influences their rate, perhaps as a result of competition for limiting factors.