Purpose To develop a deep learning model for increasing cardiac cine frame rate while maintaining spatial resolution and scan time. Materials and Methods A transformer-based model was trained and tested on a retrospective sample of cine images from 5840 patients (mean age, 55 years ± 19 [SD]; 3527 male patients) referred for clinical cardiac MRI from 2003 to 2021 at nine centers; images were acquired using 1.5- and 3-T scanners from three vendors. Data from three centers were used for training and testing (4:1 ratio). The remaining data were used for external testing. Cines with downsampled frame rates were restored using linear, bicubic, and model-based interpolation. The root mean square error between interpolated and original cine images was modeled using ordinary least squares regression. In a prospective study of 49 participants referred for clinical cardiac MRI (mean age, 56 years ± 13; 25 male participants) and 12 healthy participants (mean age, 51 years ± 16; eight male participants), the model was applied to cines acquired at 25 frames per second (fps), thereby doubling the frame rate, and these interpolated cines were compared with actual 50-fps cines. The preference of two readers based on perceived temporal smoothness and image quality was evaluated using a noninferiority margin of 10%. Results The model generated artifact-free interpolated images. Ordinary least squares regression analysis accounting for vendor and field strength showed lower error (
Abstract Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A portion of TGCT patients are refractory to cisplatin. Only 30% of patients refractory to cisplatin respond to salvage therapies while to remainder die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. We have found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). As an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer. EC cells were exquisitely sensitive to guadecitabine and the hypersensitivity was dependent on high levels of DNA methyltransferase 3B. Guadecitabine mediated transcriptional reprogramming of EC cells included induction of p53 targets and repression of pluripotency genes. As a single agent, guadecitabine completely abolished progression and induced complete regression of cisplatin resistant EC xenografts even at doses well below those required to impact somatic solid tumors. Low dose guadecitabine also sensitized refractory EC cells to cisplatin in vivo. Genome-wide analysis indicated that in vivo antitumor activity was associated with activation of p53 and immune-related pathways and the antitumor effects of guadecitabine were dependent on p53, a gene rarely mutated in TGCTs. Together, these preclinical findings provided the rationale for our recently initiated and promising phase I clinical trial using SGI-110 to treat cisplatin refractory TGCT patients. We discuss our recent genome-wide molecular studies aimed to identify potential mechanism(s) to account for the hypersensitivity of TGCTs to 5-aza including promoter demethylation, p53 activation and dsRNA MDA5/MAVS/IRF7 viral mimicry. We also discuss preliminary findings from our ongoing trial. Our findings suggest that guadecitabine alone or in combination with cisplatin is a promising strategy to treat refractory TGCT patients. Citation Format: Andrea Corbet, Costantine Albany, Emmanuel Bikorimana, Ema Khan, Jennifer Rodriguez, Brock C. Christensen, George Sandusky, Lawrence H. Einhorn, Sarah J. Freemantle, Michael J. Spinella. Low-dose demethylation therapy for the treatment of cisplatin-resistant testicular cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2999.
Introduction. Integrated clinical education (ICE), defined as clinical learning experiences embedded within the didactic portion of a DPT curriculum, is an integral component of an overall clinical education curriculum. The collaborative supervisory model has been applied to ICE experiences in DPT curricula. Two physical therapist (PT) education programs developed similar ICE experiences incorporating the collaborative model as a component of their clinical education curricula. Benefits for student learning have been described in the literature for both of these models—in isolation, but not combined. The purpose of this study was to determine factors that students felt contributed to successful team function in a collaborative ICE experience. Review of Literature. ICE can provide opportunities for students to develop knowledge, skill, and professional behaviors in preparation for full-time and final clinical experiences. There is a great deal of literature that supports the collaborative model of clinical education to facilitate teamwork and collaboration, deeper level of critical thinking and problem solving, and enhanced clinical competence. Despite the benefits of including ICE in a DPT curriculum, as well as the benefits of the collaborative model of clinical education, the physical therapy literature does not describe factors leading to successful team function when these 2 models of CE are combined. Methods and Subjects. Subjects were 51 PT student teams (3 to 4 people each) from Duke University (2 cohorts) and the University of Colorado (1 cohort) who participated in a collaborative ICE experience. Following their first 2 weeks of ICE, student teams were instructed to create a mind map that depicted how their team functioned together in the clinic. Teams utilized an online mapping tool, "Coggle It," to complete the mapping. The research team employed incident coding processes established in the literature to code the primary concepts of the team mind maps. Chi Square analysis was used to determine numeric differences across all codes among the 3 student team cohorts. Results. Twenty-four distinct codes were assigned to the primary concepts. Chi Square analysis revealed no significant differences between the 3 cohorts (P > .01) across all codes. More than 50% of teams indicated that "group dynamics" and "team communication" were vital to the effective functioning of their team in the clinic. More than 25% of the teams included "individual student qualities," "the learning environment," "practicing skills," "the instructor's teaching strategies," "adult learner characteristics," and the "clinical instructor" of key importance. From the data, 4 themes emerged as being important for effective collaborative learning in an ICE: The Team, the Clinical Environment, the Individual Student, and the Clinical Instructor. Discussion and Conclusion. The 4 themes identified in this study contribute to the literature surrounding student learning in clinical education, specifically a collaborative ICE experience. This study suggests that these characteristics are important for positive experiences and should be factors that are considered by both academic programs and clinical instructors when designing, implementing, and teaching in a collaborative ICE experience.
Introduction: Vitamin D has been shown to play an important role as an immune-modulator. Vitamin D insufficiency has been implicated in up to 50% of critically ill patients. Recently it has been shown to be a predictor of both short and long term mortality in the critically ill; however, no studies have determined if vitamin D insufficiency is associated with worse outcomes in severe sepsis and septic shock. Hypothesis: Vitamin D insufficient (VDI) patients with severe sepsis and septic shock will have worse outcomes than vitamin D sufficient (VDS) patients. Methods: A retrospective cohort study conducted in an urban, academic tertiary care center. All severe sepsis or septic shock patients from June 2006 to April 2011 with a 25-hydroxyvitamin D (25-OH D) level ±30 days of admission were evaluated. Baseline demographics included age, race, gender, comorbidities, source of infection, APACHE II, 25-OH D levels and vitamin D supplementation. Outcome data included hospital and intensive care unit (ICU) length of stay (LOS) and hospital, 30 day and 90 day mortality. Univariate analysis with Chi-square, Fisher’s exact test or t-test was performed. Multivariate analysis was conducted. Results: Of the 2015 septic patients admitted during the enrollment period, 121 had 25-OH D levels within 30 days of admission [56 patients (46%) 25-OH D > 15 ng/mL, VDS; 65 patients (54%) =15 ng/mL, VDI]. Baseline demographics were similar, except there were more African Americans in the VDI group (P<0.01). There was no difference in hospital mortality (24.6% VDI vs. 21.4 % VDS, P=0.68) or 30 day mortality (35.4% VDI vs. 19.6% VDS, P=0.06). 90 day mortality was higher in VDI patients compared to VDS (43.1% vs. 23.2%, P= 0.02), and remained a significant predictor of 90 day mortality (P=0.02) in the multivariate analysis. ICU LOS was longer in the VDI group (12.9 ± 15.5 days vs. 7.6 ± 6.7 days, P=0.02). Conclusions: This study demonstrates that patients with vitamin D insufficiency had higher 90 day mortality and increased ICU length of stay. Further research is warranted to elucidate these outcomes.
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