Feasibility of a Readiness Exam for Predicting Radiography Program Success: A Pilot Study

ABSTRACT Background: Research investigating predictors of academic success in rigorous health science education is valuable for curricular intervention for identified at-risk students. Various predictors of success have been investigated, but the literature is insufficient when examining anatomy and physiology readiness scores as they correlate to radiography curricular success. This pilot study assessed the correlation between readiness exam scores and programmatic course GPA to determine if the scores could be used as a metric for identifying academic success resources for incoming students. Cohorts of the radiography program at a midwestern health sciences center demonstrated a longitudinal trend of difficulty with anatomy and physiology programmatic coursework. Therefore, researchers set out to investigate whether or not readiness exam scores, in addition to the metrics they were already utilizing, could be used as a tool for early academic remediation. Objective: The objective of this study was to determine if the anatomy and physiology readiness exam scores would be reliable indicators of programmatic success in anatomy and physiology program coursework. Design: This investigation occurred in two phases: a retrospective correlational phase and a quasi-experimental phase. Methods: Retrospective data from cohorts that matriculated between 2013 and 2017 (n=91) was collected and de-identified. Data included prerequisite grade point average (GPA) and grades from anatomy and physiology course taken during the program. During the quasi-experimental phase, a sample of students (n=18) completed a readiness examination. The scores from this examination were correlated with prerequisite GPA and program anatomy and physiology GPA. Results: Data analysis revealed prerequisite GPA and the anatomy and physiology section of the readiness examination to be strong and moderate predictors of programmatic anatomy and physiology course grades, respectively. Conclusion: Predictors of curricular success in a radiography program’s anatomy and physiology coursework are essential factors to consider in relation to admissions practices, curricular prerequisite standards, and on-boarding of new students, especially those identified as at-risk

Should Pharma Companies Waive Their COVID-19 Vaccine Patents? A Legal and Ethical Appraisal

Pharmaceutical companies, like many other types of companies, are incentivized to create, manufacture, and distribute new products, in part due to the legal protections of patent law. However, the tension between patent rights and the public good has been heightened as pharma companies developed new vaccines to combat the COVID-19 pandemic. Wealthy governments paid well for vaccines and received ample supplies, while low- and middle-income countries struggled to obtain access to any vaccines. Some countries called for pharmaceutical companies to waive their patent protections for vaccines in order to facilitate the worldwide manufacture and distribution of COVID-19 vaccines. This paper will examine the rationale of patent protection and patent waiver issues, then compare these concepts with ethical constructs and a Jewish perspective

High-fidelity single-shot readout for a spin qubit via an enhanced latching mechanism

The readout of semiconductor spin qubits based on spin blockade is fast but suffers from a small charge signal. Previous work suggested large benefits from additional charge mapping processes, however uncertainties remain about the underlying mechanisms and achievable fidelity. In this work, we study the single-shot fidelity and limiting mechanisms for two variations of an enhanced latching readout. We achieve average single-shot readout fidelities > 99.3% and > 99.86% for the conventional and enhanced readout respectively, the latter being the highest to date for spin blockade. The signal amplitude is enhanced to a full one-electron signal while preserving the readout speed. Furthermore, layout constraints are relaxed because the charge sensor signal is no longer dependent on being aligned with the conventional (2, 0) - (1, 1) charge dipole. Silicon donor-quantum-dot qubits are used for this study, for which the dipole insensitivity substantially relaxes donor placement requirements. One of the readout variations also benefits from a parametric lifetime enhancement by replacing the spin-relaxation process with a charge-metastable one. This provides opportunities to further increase the fidelity. The relaxation mechanisms in the different regimes are investigated. This work demonstrates a readout that is fast, has one-electron signal and results in higher fidelity. It further predicts that going beyond 99.9% fidelity in a few microseconds of measurement time is within reach.Comment: Supplementary information is included with the pape

Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells

AbstractEngineered nanoparticles have the potential to expand the breadth of pulmonary therapeutics, especially as respiratory vaccines. Notably, cationic nanoparticles have been demonstrated to produce superior local immune responses following pulmonary delivery; however, the cellular mechanisms of this increased response remain unknown. To this end, we investigated the cellular response of lung APCs following pulmonary instillation of anionic and cationic charged nanoparticles. While nanoparticles of both surface charges were capable of trafficking to the draining lymph node and were readily internalized by alveolar macrophages, both CD11b and CD103 lung dendritic cell (DC) subtypes preferentially associated with cationic nanoparticles. Instillation of cationic nanoparticles resulted in the upregulation of Ccl2 and Cxc10, which likely contributes to the recruitment of CD11b DCs to the lung. In total, these cellular mechanisms explain the increased efficacy of cationic formulations as a pulmonary vaccine carrier and provide critical benchmarks in the design of pulmonary vaccine nanoparticles.From the Clinical EditorAdvance in nanotechnology has allowed the production of precise nanoparticles as vaccines. In this regard, pulmonary delivery has the most potential. In this article, the authors investigated the interaction of nanoparticles with various types of lung antigen presenting cells in an attempt to understand the cellular mechanisms. The findings would further help the future design of much improved vaccines for clinical use

Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization

To our knowledge, no other nano-based vaccine delivery platform has directly assessed the effects of nanoparticle charge on pulmonary vaccination without affecting other physio/chemical particle characteristics and/or antigen loading. The Particle Replication in Non-Wetting Templates nanoparticle fabrication process is unique in that it allows for isolation of charge as the sole variable in these studies while maintaining all other physical and chemical parameters constant. We find that positively charged nanoparticles induce robust mucosal and systemic antibody responses following pulmonary administration, whereas negatively charged nanoparticles fail to do so. Therefore, our studies underscore the importance of considering nanoparticle charge as a critical design parameter when generating pulmonary-based vaccines and may have implications for particulate vaccination through other routes of administration

Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model

Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of inherent cytotoxic or immunostimulatory properties. Therefore, determining baseline immune responses to nanomaterials is of utmost importance when designing human therapeutics. We characterized the response of human immune cells to hydrogel NPs fabricated using Particle Replication in Non-wetting Templates (PRINT) technology. We found preferential NP uptake by primary CD14+ monocytes, which was significantly reduced upon PEGylation of the NP surface. Multiplex cytokine analysis of NP treated primary human peripheral blood mononuclear cells (hu-PBMC) suggests that PRINT based hydrogel NPs do not evoke significant inflammatory responses nor do they induce cytotoxicity or complement activation. We furthered these studies using an in vivo humanized mouse model and similarly found preferential NP uptake by human CD14+ monocytes without systemic inflammatory cytokine responses. These studies suggest that PRINT hydrogel particles form a desirable platform for vaccine and drug delivery as they neither induce inflammation nor toxicity

Distribution and Cellular Uptake of PEGylated Polymeric Particles in the Lung Towards Cell-Specific Targeted Delivery

We evaluated the role of a poly(ethylene glycol) (PEG) surface coating to increase residence times and alter the cellular fate of nano- and microparticles delivered to the lung

Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex

Ciclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and hematologic malignancies. Its clinical utility as an oral anticancer agent, however, is limited by poor oral bioavailability and gastrointestinal toxicity. Fosciclopirox, the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration. We characterized the activity of CPX-POM and its major metabolites in in vitro and in vivo preclinical models of high-grade urothelial cancer. CPX inhibited cell proliferation, clonogenicity and spheroid formation, and increased cell cycle arrest at S and G0/G1 phases. Mechanistically, CPX suppressed activation of Notch signaling. Molecular modeling and cellular thermal shift assays demonstrated CPX binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. To establish in vivo preclinical proof of principle, we tested fosciclopirox in the validated N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) mouse bladder cancer model. Once-daily intraperitoneal administration of CPX-POM for four weeks at doses of 235 mg/kg and 470 mg/kg significantly decreased bladder weight, a surrogate for tumor volume, and resulted in a migration to lower stage tumors in CPX-POM treated animals. This was coupled with a reduction in the proliferation index. Additionally, there was a reduction in Presenilin 1 and Hes-1 expression in the bladder tissues of CPX-POM treated animals. Following the completion of the first-in-human Phase 1 trial (NCT03348514), the pharmacologic activity of fosciclopirox is currently being characterized in a Phase 1 expansion cohort study of muscle-invasive bladder cancer patients scheduled for cystectomy (NCT04608045) as well as a Phase 2 trial of newly diagnosed and recurrent urothelial cancer patients scheduled for transurethral resection of bladder tumors (NCT04525131)

Regional Systems of Care Demonstration Project: American Heart Association Mission: Lifeline STEMI Systems Accelerator.

BACKGROUND: Up to 50% of patients fail to meet ST-segment-elevation myocardial infarction (STEMI) guideline goals recommending a first medical contact-to-device time of <90 minutes for patients directly presenting to percutaneous coronary intervention-capable hospitals and <120 minutes for transferred patients. We sought to increase the proportion of patients treated within guideline goals by organizing coordinated regional reperfusion plans. METHODS: We established leadership teams, coordinated protocols, and provided regular feedback for 484 hospitals and 1253 emergency medical services (EMS) agencies in 16 regions across the United States. RESULTS: Between July 2012 and December 2013, 23 809 patients presented with acute STEMI (direct to percutaneous coronary intervention hospital: 11 765 EMS transported and 6502 self-transported; 5542 transferred). EMS-transported patients differed from self-transported patients in symptom onset to first medical contact time (median, 47 versus 114 minutes), incidence of cardiac arrest (10% versus 3%), shock on admission (11% versus 3%), and in-hospital mortality (8% versus 3%; P<0.001 for all comparisons). There was a significant increase in the proportion of patients meeting guideline goals of first medical contact-to-device time, including those directly presenting via EMS (50% to 55%; P<0.001) and transferred patients (44%-48%; P=0.002). Despite regional variability, the greatest gains occurred among patients in the 5 most improved regions, increasing from 45% to 57% (direct EMS; P<0.001) and 38% to 50% (transfers; P<0.001). CONCLUSIONS: This Mission: Lifeline STEMI Systems Accelerator demonstration project represents the largest national effort to organize regional STEMI care. By focusing on first medical contact-to-device time, coordinated treatment protocols, and regional data collection and reporting, we were able to increase significantly the proportion of patients treated within guideline goals