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Our team is reviewing tools and techniques that enable rapid prototyping. Generative Adversarial Networks (GANs) have been shown to reduce training requirements for detection problems. GANs compete generative and discriminative classifiers to improve detection performance. This paper expands the use of GANs from detection (k=2) to classification (k>2) problems. Several GAN network structures and training set sizes were compared to the baseline discriminative network and Bayes' classifiers. The results show no significant performance differences among any of the network configurations or training set size trials. However, the GANs trained with fewer network nodes and iterations than needed by the discriminator classifiers alone.

BACKGROUND: Prolonged dual antiplatelet therapy (DAPT) is recommended after an acute myocardial infarction (AMI) to reduce ischemic events but is associated with increased rates of major and minor bleeding. OBJECTIVES: This study sought to determine the incidence of post-percutaneous coronary intervention (PCI) bleeding that occurs on contemporary DAPT and its impact on quality of life (QOL). METHODS: We studied 9,290 AMI patients treated with PCI and discharged alive between April 2010 and September 2012. Post-discharge bleeding was categorized according to the Bleeding Academic Research Consortium (BARC) definition. The primary outcome was the 6-month Euro QOL–5 Dimension (EQ-5D) index score (a measure of health utility); a secondary outcome was the EQ-5D visual analog scale (VAS) at 6 months. RESULTS: Of the 9,290 patients with AMI, bleeding events occurred as follows: any BARC bleeding: 24.2%; BARC 1: 9.1%; BARC 2: 13.8%; BARC 3: 1.1%; BARC 4: 0.03%; and BARC 5: 0%. Those who experienced any BARC bleeding had lower scores across all 5 EQ-5D domains (mobility, self-care, usual activities, pain, and anxiety), as well as lower EQ-5D VAS and EQ-5D index scores. After clinical risk adjustment, any BARC bleeding was independently associated with 6-month EQ-5D index score (p < 0.0001) and lower QOL (p < 0.001). Both the EQ-5D index and the VAS score declined in a stepwise fashion with increasing BARC severity. CONCLUSIONS: Among patients undergoing PCI for AMI, bleeding during follow-up was associated with worse 6-month utility and QOL. Although even minor bleeding was associated with impaired health status and QOL, the degree of impairment increased in a stepwise fashion with bleeding severity.

Many antibiotics bind the bacterial ribosome, the only validated RNA target. Derivatizing or mimicking these natural products is a potential way to create new RNA binders or antibacterials overcoming bacterial resistance. This motivated this work, which addressed the preparation of new RNA binders and the development of new assays. Semi -synthetic derivatives of clinically useful aminoglycosides, tobramycin and amikacin, were prepared by selectively modifying their 6'' positions. The binding to the rRNA A-site was probed by an in vitro Förster resonance energy transfer (FRET)-based assay, and antibacterial activity was quantified by determining minimum inhibitory concentrations (MICs). Most analogs displayed greater affinities for the bacterial A-site compared to the parent compounds. Several amikacin analogs showed potent and broad-spectrum antibacterial activity against resistant bacteria, suggesting they are overcoming resistance mechanisms. However, tobramycin analogs exhibited overall poor antibacterial activity. As an alternative approach to potentially new RNA binders, mimetics of the aminoglycoside pharmacophore, 2- deoxystreptamine, were synthesized. In noting structural similarities to aminoglycosides, polymyxin antibiotics, which target the cell wall, were examined as rRNA binders using a FRET assay. The polymyxins showed significant affinity for to the bacterial and eukaryotic A-sites. Additionally, in vitro translation assays showed all polymyxins interfered with eukaryotic translation, but not with bacterial, which could account for toxicity effects. Fluorescent molecules and labeled oligonucleotides are valuable tools to probe small molecule, RNA, and protein interactions. We have developed assays utilizing isomorphic fluorescent nucleosides to study RNA catalysis and small molecule-enzyme interactions. A fluorescent guanosine analog, thG triphosphate, was incorporated into oligonucleotides by T7 RNA polymerase. Additionally, modified transcripts were used to assemble a hammerhead ribozyme containing enzyme and substrate strands with thG replacing guanosine. The thG modified substrate was effectively cleaved by the natural enzyme. However, the thG modified enzyme showed no cleavage ability, suggesting the modifications likely disrupted the catalytic center. Toward exploring protein-nucleoside interactions with fluorescent nucleoside analogs, a fluorescent adenosine derivative, thA, was found to be deaminated by the enzyme adenosine deaminase (ADA) into the corresponding fluorescent inosine derivative, thI. A high-throughput assay utilizing the fluorescent properties of these molecules to discover ADA inhibitors was developed

Adenosine deaminase, a major enzyme involved in purine metabolism, converts an isomorphic fluorescent analogue of adenosine (thA) to an isomorphic inosine analogue (thI), which possesses distinct spectral features, allowing one to monitor the enzyme-catalyzed reaction and its inhibition in real time. The utility of this sensitive fluorescently-monitored transformation for the high throughput detection and analysis of ADA inhibitors is demonstrated.

ObjectivesThe aim of this study was to determine diagnostic testing patterns after percutaneous coronary intervention (PCI).BackgroundLittle is known about patterns of diagnostic testing after PCI in the United States or the relationship of these patterns to clinical outcomes.MethodsCenters for Medicare and Medicaid Services inpatient and outpatient claims were linked to National Cardiovascular Data Registry CathPCI Registry data from 2005 to 2007. Hospital quartiles of the cumulative incidence of diagnostic testing use within 12 and 24 months after PCI were compared for patient characteristics, repeat revascularization, acute myocardial infarction, and death.ResultsA total of 247,052 patients underwent PCI at 656 institutions. Patient and site characteristics were similar across quartiles of testing use. There was a 9% and 20% higher adjusted risk for repeat revascularization in quartiles 3 and 4 (highest testing rate), respectively, compared with quartile 1 (lowest testing rate) (p = 0.020 and p < 0.0001, respectively). The adjusted risk for death or acute myocardial infarction did not differ among quartiles.ConclusionsAlthough patient characteristics were largely independent of rates of post-PCI testing, higher testing rates were not associated with lower risk for myocardial infarction or death, but repeat revascularization was significantly higher at these sites. Additional studies should examine whether increased testing is a marker for improved quality of post-PCI care or simply increased health care utilization.

An eight-week weight-loss competition was conducted in an industrial worksite in Big Island, Virginia in the spring of 1993. Educational interventions were based on theories of self-efficacy and social support. Sixteen employees volunteered for the weight loss competition; fifteen completed the program. A single case study design was used to analyze the relationships among self-efficacy, intake of dietary fat, and weight loss as impact variables. Process variables deemed important for the program’s success were also examined for each individual. They included attendance at weekly weigh-ins, completion of daily food intake forms, attendance at weekly educational sessions, and completion of self-efficacy questionnaires. Results showed that women were more likely to participate in the program’s activities than men. Teams that worked together (within the same department) were more successful and more supportive of each other than teams composed of individuals from different departments. Individuals who participated in the educational sessions and competed in the assignments were more successful in losing weight. Due to the small number of participants, no significant effect was found between self-efficacy scores and weight loss. Master of Science

BackgroundThere has been a decline in hospital length of stay (LOS) after primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI).ObjectivesThe objective of this study was to examine whether shorter LOS is safe for older patients undergoing PPCI for STEMI.MethodsThe study analyzed patients’ characteristics and 30-day outcomes by LOS (short, ≤3 days; medium, 4 to 5 days; long >5 days; where LOS was the discharge date minus the admission date plus 1) among 33,920 patients with STEMI in the linked CathPCI Registry-Centers for Medicare & Medicaid Services dataset who were ≥65 years of age and treated with PPCI from 2004 to 2009.ResultsPercents of patients in each category were as follows: 26.9%, 46.3%, and 26.8% for short, medium, and long LOS, respectively. Patients with a long LOS were generally older, female, and had more comorbidities, including cardiogenic shock and multivessel disease. Patients with a short LOS generally had higher ejection fraction and single-vessel disease. There was no significant difference in 30-day all-cause mortality (hazard ratio [HR]: 1.00; 95% confidence interval [CI]: 0.74 to 1.34) or major adverse cardiac events (MACE) (death, readmission for myocardial infarction, unplanned revascularization: HR: 1.03; 95% CI: 0.86 to 1.25) for medium versus short LOS. There was a significant increase in adjusted mortality (HR: 2.30; 95% CI: 1.72 to 3.07) and MACE (HR: 1.75; 95% CI: 1.44 to 2.12) for long versus short LOS. Patients with a very short LOS (1 to 2 days) had significantly increased 30-day mortality and MACE compared with a 3- to 4-day LOS.ConclusionsPatients discharged as early as 48 h after PPCI have outcomes similar to patients who stay in the hospital for 4 to 5 days. Early, but not very early (

ObjectivesThis study sought to develop a model that predicts bleeding complications using an expanded bleeding definition among patients undergoing percutaneous coronary intervention (PCI) in contemporary clinical practice.BackgroundNew knowledge about the importance of periprocedural bleeding combined with techniques to mitigate its occurrence and the inclusion of new data in the updated CathPCI Registry data collection forms encouraged us to develop a new bleeding definition and risk model to improve the monitoring and safety of PCI.MethodsDetailed clinical data from 1,043,759 PCI procedures at 1,142 centers from February 2008 through April 2011 participating in the CathPCI Registry were used to identify factors associated with major bleeding complications occurring within 72 h post-PCI. Risk models (full and simplified risk scores) were developed in 80% of the cohort and validated in the remaining 20%. Model discrimination and calibration were assessed in the overall population and among the following pre-specified patient subgroups: females, those older than 70 years of age, those with diabetes mellitus, those with ST-segment elevation myocardial infarction, and those who did not undergo in-hospital coronary artery bypass grafting.ResultsUsing the updated definition, the rate of bleeding was 5.8%. The full model included 31 variables, and the risk score had 10. The full model had similar discriminatory value across pre-specified subgroups and was well calibrated across the PCI risk spectrum.ConclusionsThe updated bleeding definition identifies important post-PCI bleeding events. Risk models that use this expanded definition provide accurate estimates of post-PCI bleeding risk, thereby better informing clinical decision making and facilitating risk-adjusted provider feedback to support quality improvement.

ObjectivesThis study sought to compare in-hospital mortality and bleeding complications for procedures performed by sleep-deprived versus non–sleep-deprived operators.BackgroundTo optimize the safety of percutaneous coronary intervention (PCI), it is essential to determine whether physicians performing emergent, middle-of-the-night procedures, and who may be sleep-deprived as a consequence, have equally safe outcomes when performing cases the following day.MethodsWe used CathPCI registry data to compare in-hospital mortality and bleeding complications for procedures performed by sleep-deprived versus non–sleep-deprived operators using logistic regression with generalized estimating equations to account for within-operator clustering. Outcomes were risk-adjusted using previously validated models for in-hospital mortality and bleeding. Our cohort included 1,509,096 daytime PCI procedures performed by 5,014 operators between 7 am and midnight from July 1, 2009, through June 30, 2012. Operators were assumed to be acutely sleep-deprived if they began a middle-of-the-night PCI between midnight and 6:59 am and performed a next-day PCI between 7 am and midnight, and chronically sleep deprived if they had performed multiple middle-of-the-night PCI procedures during the previous 7 days.ResultsOnly 2.4% of all daytime PCI procedures were performed by operators who had performed at least 1 middle-of-the-night PCI procedure earlier that day. In adjusted analyses, when comparing procedures performed by acutely sleep-deprived with non–sleep-deprived operators, there were no significant differences in mortality (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 0.94 to 1.12; p = 0.61) or bleeding (OR: 1.03, 95% CI: 0.98 to 1.08; p = 0.19). However, a greater degree of chronic sleep deprivation was associated with a higher adjusted risk of bleeding (OR: 1.19, 95% CI: 1.05 to 1.34; p = 0.007).ConclusionsDaytime PCI procedures are uncommonly performed by sleep-deprived operators. We found no signal of increased complications when acutely sleep-deprived operators performed PCI but an increased risk of bleeding associated with procedures performed by operators with greater degrees of chronic sleep deprivation.

Background Little is known about patients with severe symptomatic aortic stenosis (AS) who receive medical management despite evaluation at a heart valve treatment center. Objective We identified patient characteristics associated with medical management, physician-reported reasons for selecting medical management, and patients’ perceptions of their involvement and satisfaction with treatment selection. Methods and results Of 454 patients evaluated for AS at 9 established heart valve treatment centers from December 12, 2013 to August 19, 2014, we included 407 with severe symptomatic AS. Information was collected using medical record review and survey of patients and treating physicians. Of 407 patients, 212 received transcatheter aortic valve replacement (TAVR), 124 received surgical aortic valve replacement (SAVR), and 71 received medical management (no SAVR/TAVR). Thirty-day predicted mortality was higher in patients receiving TAVR (8.7%) or medical management (9.8%) compared with SAVR (3.4%) (P

Little is known about patients with severe symptomatic aortic stenosis (AS) who receive medical management despite evaluation at a heart valve treatment center.