TCT-804 Outcomes of Trans-Carotid TAVR in a high-Volume Center

Background Although the preferred route for transcatheter aortic valve replacement is through the femoral artery, alternatives remain necessary for patients with obstructive iliofemoral disease. Our valve team has developed a large experience using the carotid artery as a primary alternative vascular access approach for transcatheter aortic valve replacement (TAVR). We aim to compare short-term outcomes by access route in a single-center, high-volume, transcarotid (TC) TAVR program. Methods All patients undergoing TAVR between September 2012 and September 2018 were included in the study. Baseline demographics and outcomes were obtained from data our institution submitted in compliance with TVT (Transcatheter Valve Therapy) reporting and are supplemented by individual chart review. Results Overall, 1,153 commercial TAVR procedures were completed during the study period. Of these, 976 (85%) were transfemoral (TF), 105 (9%) were TC, and 72 (6%) were other (53 transapical, 14 transaxillary, 5 transaortic). TF patients had lower Society of Thoracic Surgeons (STS) scores (6.0% vs. 7.1% vs. 8.3%), peripheral vascular disease (24% vs. 88% vs. 72%), and cerebral vascular disease (11% vs. 17% vs. 32%) compared with TC and other patients, respectively (p \u3c 0.001). Combined in-hospital and 30-day mortality was 2.6% for the TF cohort versus 3.8% for TC (p = 0.36) and 13.9% for other (p \u3c 0.001). The stroke rate at 30 days was 3.7% for TF versus 3.8% for TC and 4.2% for other access routes (p = 0.98) (Table). Conclusion TAVR can be safely performed from the TC access route at a high-volume center with similar in-hospital and 30-day mortality and stroke rates compared with TF patients. Mortality was significantly increased, however, in patients treated with other alternative access routes

Field Demonstration of a Real-time Non-intrusive Monitoring System for Condition-based Maintenance

The performance of important electrical loads on mission critical systems like warships or off-shore platforms is often tracked by dedicated monitoring equipment. Individual monitoring of each load is expensive and risky. Expense occurs because of the need for individual sensors and sensor wiring for every load of interest. Reliability is compromised because detected failures or fault conditions might legitimately be due to load failure, but might also be due to errors or failure in the sensor network or recording instruments. The power distribution network on a warship could be pressed into “dual-use” service, providing not only power distribution but also a diagnostic monitoring capability based on observations of the way in which loads draw power from the distribution service. This paper describes field tests of a prototype system that monitors multiple loads using existing electrical wiring. Initial results are presented from a device that monitors a small collection of motors and two other devices that monitor an entire engine room.Grainger Foundation; National Science Foundation (U.S.); United States. National Aeronautics and Space Administration; United States. Coast Guard; United States. Office of Naval Research. Electric Ship Research and Development Consortium; NAVSEA; University of North Carolin

Concert recording 2014-04-08

[Track 01]. Madama Butterfly. Un bel di vedremo / Glacomo Puccini -- [Track 02]. Hello again. Tom / Michael John LaCiusa -- [Track 03]. Mein schoner stern! (my lovely star) / Robert Schumann -- [Track 04]. Into the night / Robert Schumann -- [Track 05]. Per la Gloria / Giovanni B. Bonocirii -- [Track 06]. Bonjour, Suzon! / Leo Delibes -- [Track 07]. Die Winterreise. Erstarrung (numbness) / Franz Schubert -- [Track 08]. West Side Story. Something\u27s coming / Leonard Bernstein -- [Track 09]. Un ballo in maschera. Saper vorreste / Giuseppe Verdi -- [Track 10]. O del mio amato ben / Stefeno Donaudy -- [Track 11]. O del mio dolce ardor / Christoph W. von Gluck -- [Track 12]. My fair lady. I could have danced all night / Loewe & Lerner -- [Track 13]. Vergebliches standchen (The vain suit) / Johannes Brahms

A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients

An analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization–triple quadrupole–tandem mass spectrometry. Patient plasma samples spiked with the internal standard methotrexate were measured by multiple reaction monitoring. The detection limit was 0.4 fmol/μL, lower limit of quantification was 0.9 fmol/μL, and upper limit of quantification was 60 fmol/μL, respectively. Overall observed pemetrexed concentrations in patient samples ranged between 8.7 (1.4) and 142.7 (20.3) pmol/μL (SD). The newly developed mass spectrometric assay is applicable for (routine) therapeutic drug monitoring of pemetrexed concentrations in plasma from non-small cell lung cancer patients

Early-life stress biases responding to negative feedback and increases amygdala volume and vulnerability to later-life stress

Early-life stress (ELS) or adversity, particularly in the form of childhood neglect and abuse, is associated with poor mental and physical health outcomes in adulthood. However, whether these relationships are mediated by the consequences of ELS itself or by other exposures that frequently co-occur with ELS is unclear. To address this question, we carried out a longitudinal study in rats to isolate the effects of ELS on regional brain volumes and behavioral phenotypes relevant to anxiety and depression. We used the repeated maternal separation (RMS) model of chronic ELS, and conducted behavioral measurements throughout adulthood, including of probabilistic reversal learning (PRL), responding on a progressive ratio task, sucrose preference, novelty preference, novelty reactivity, and putative anxiety-like behavior on the elevated plus maze. Our behavioral assessment was combined with magnetic resonance imaging (MRI) for quantitation of regional brain volumes at three time points: immediately following RMS, young adulthood without further stress, and late adulthood with further stress. We found that RMS caused long-lasting, sexually dimorphic biased responding to negative feedback on the PRL task. RMS also slowed response time on the PRL task, but without this directly impacting task performance. RMS animals were also uniquely sensitive to a second stressor, which disproportionately impaired their performance and slowed their responding on the PRL task. MRI at the time of the adult stress revealed a larger amygdala volume in RMS animals compared with controls. These behavioral and neurobiological effects persisted well into adulthood despite a lack of effects on conventional tests of 'depression-like' and 'anxiety-like' behavior, and a lack of any evidence of anhedonia. Our findings indicate that ELS has long-lasting cognitive and neurobehavioral effects that interact with stress in adulthood and may have relevance for understanding the etiology of anxiety and depression in humans

A methylation risk score for chronic kidney disease: a HyperGEN study

Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead