1001–24 Local Delivery of Urokinase to Porcine Coronary Arteries Using the Localmed Infusion Sleeve

Local Delivery of thrombolytic agents may reduce thrombus formation after balloon angioplasty. The Localmed Infusion Sleeve enables localized infusion of urokinase to be performed at the time of balloon angioplasty without the need for catheter exchange.MethodsBalloon angioplasty was performed on 13 coronary arteries of 5 pigs at 4 atmospheres with a balloon to artery ratio of approximately 1.1 to 1. After angioplasty the Infusion Sleeve was advanced over the dilatation balloon and the balloon was reinflated to 2 atmospheres to appose the sleeve to the vessel wall. 50,000 Units (8 cc) of 123l-urokinase was infused through the microperforations in the sleeve for 10 seconds by a computer controlled pump. The coronaries were then excised and counted in a gamma counter.ResultsConclusions(1) The Localmed Infusion Sleeve enables drug infusion to be uncoupled from balloon dilatation. (2) Successful delivery of Urokinase to the vessel wall may be achieved using this device without the need for catheter exchange. (3) Persistence of urokinase within the vessel wall occurs after local delivery

Frame-Dragging Vortexes and Tidal Tendexes Attached to Colliding Black Holes: Visualizing the Curvature of Spacetime

When one splits spacetime into space plus time, the spacetime curvature (Weyl tensor) gets split into an "electric" part E_{jk} that describes tidal gravity and a "magnetic" part B_{jk} that describes differential dragging of inertial frames. We introduce tools for visualizing B_{jk} (frame-drag vortex lines, their vorticity, and vortexes) and E_{jk} (tidal tendex lines, their tendicity, and tendexes), and also visualizations of a black-hole horizon's (scalar) vorticity and tendicity. We use these tools to elucidate the nonlinear dynamics of curved spacetime in merging black-hole binaries.Comment: 4 pages, 5 figure

Growth References for Tsimane Forager-Horticulturalists of the Bolivian Amazon

Objectives—Growth standards and references currently used to assess population and individual health are derived primarily from urban populations, including few individuals from indigenous or subsistence groups. Given environmental and genetic differences, growth may vary in these populations. Thus, there is a need to assess whether international standards are appropriate for all populations, and to produce population specific references if growth differs. Here we present and assess growth references for the Tsimane, an indigenous population of Bolivian forager-horticulturalists. Methods—Mixed cross-sectional/longitudinal anthropometrics (9,614 individuals; 30,118 observations; ages 0–29 years) were used to generate centile curves and Lambda-Mu-Sigma (LMS) tables for height-for-age, weight-for-age, body mass index (BMI)-for-age, and weight-for-height (WFH) using Generalized Additive Models for Location Shape and Scale (GAMLSS). Velocity curves were generated using SuperImposition by Translation and Rotation (SITAR). Tsimane ≤5 years were compared World Health Organization (WHO) standards while those \u3e5 years were compared to WHO school age references. All ages were compared to published references for Shuar forager-horticulturalists of the Ecuadorian Amazon. Results—Tsimane growth differs from WHO values in height and weight, but is similar for BMI and WFH. Tsimane growth is characterized by slow height velocity in childhood and early adolescent peak height velocity at 11.3 and 13.2 years for girls and boys. Tsimane growth patterns are similar to Shuar, suggesting shared features of growth among indigenous South Americans. Conclusions—International references for BMI-for-age and WFH are likely appropriate for Tsimane, but differences in height-for-age and weight-for-age suggest Tsimane specific references may be useful for these measures

A Topcolor Jungle Gym

We discuss an alternative to the topcolor seesaw mechanism. In our scheme, all the light quarks carry topcolor, and there are many composite SU(2) doublets. This makes it possible to get the observed top quark mass and observed $SU(2) \times U(1)$ breaking in a way that is quite different from the classic seesaw mechanism. We discuss a model of this kind that arises naturally in the context of dynamically broken topcolor. There are many composite scalars in a theory of this kind. This has important effects on the Pagels-Stokar relation and the Higgs mass. We find $m_{\rm Higgs} < 330$ GeV, lighter than in typical topcolor models. We also show that the electroweak singlet quarks in such a model can be lighter than the corresponding quarks in a seesaw model.Comment: 23 pages, LaTeX, uses epsf and psfi

Intensive swift and LCO monitoring of PG 1302–102 : active galactic nucleus disk reverberation mapping of a supermassive black hole binary candidate

This work is supported by the NANOGrav National Science Foundation Physics Frontiers Center award No. 2020265 and NASA grant 80NSSC24K0251. Research at UC Irvine was supported by NSF grant AST-1907290. E.M.C. gratefully acknowledges support from the NSF through grant No. AST-1909199.We present an intensive multiwavelength monitoring campaign of the quasar PG 1302−102 with Swift and the Las Cumbres Observatory network telescopes. At z ∼ 0.3, it tests the limits of the reverberation mapping (RM) technique in probing the accretion disk around a supermassive black hole (SMBH) and extends the parameter space to high masses and high accretion rates. This is also the first time the RM technique has been applied to test disk structures predicted in the SMBH binary model that has been suggested for this source. PG 1302−102 was observed at a ∼daily cadence for ∼9 months in 14 bands spanning from X-ray to UV and optical wavelengths, and it shows moderate to significant levels of variability correlated between wavelengths. We measure the interband time lags, which are consistent with a τ ∝ λ 4/3 relation as expected from standard disk reprocessing, albeit with large uncertainties. The disk size implied by the lag spectrum is consistent with the expected disk size for its black hole mass within uncertainties. While the source resembles other reverberation-mapped active galactic nuclei in many respects, and we do not find evidence supporting the prevalent hypothesis that it hosts an SMBH binary, we demonstrate the feasibility of studying SMBH binaries from this novel angle and suggest possibilities for the LSST Deep Drilling Fields.Peer reviewe

Do Wealth and Inequality Associate with Health in a Small-Scale Subsistence Society?

In high-income countries, one’s relative socio-economic position and economic inequality may affect health and well-being, arguably via psychosocial stress. We tested this in a small-scale subsistence society, the Tsimane, by associating relative household wealth (n = 871) and community-level wealth inequality (n = 40, Gini = 0.15–0.53) with a range of psychological variables, stressors, and health outcomes (depressive symptoms [n = 670], social conflicts [n = 401], non-social problems [n = 398], social support [n = 399], cortisol [n = 811], body mass index [n = 9,926], blood pressure [n = 3,195], self-rated health [n = 2523], morbidities [n = 1542]) controlling for community-average wealth, age, sex, household size, community size, and distance to markets. Wealthier people largely had better outcomes while inequality associated with more respiratory disease, a leading cause of mortality. Greater inequality and lower wealth were associated with higher blood pressure. Psychosocial factors did not mediate wealth-health associations. Thus, relative socio-economic position and inequality may affect health across diverse societies, though this is likely exacerbated in high-income countries

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

The effect of LRRK2 loss-of-function variants in humans

Analysis of large genomic datasets, including gnomAD, reveals that partial LRRK2 loss of function is not strongly associated with diseases, serving as an example of how human genetics can be leveraged for target validation in drug discovery. Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models of human gene inactivation and can be valuable indicators of gene function and the potential toxicity of therapeutic inhibitors targeting these genes(1,2). Gain-of-kinase-function variants in LRRK2 are known to significantly increase the risk of Parkinson's disease(3,4), suggesting that inhibition of LRRK2 kinase activity is a promising therapeutic strategy. While preclinical studies in model organisms have raised some on-target toxicity concerns(5-8), the biological consequences of LRRK2 inhibition have not been well characterized in humans. Here, we systematically analyze pLoF variants in LRRK2 observed across 141,456 individuals sequenced in the Genome Aggregation Database (gnomAD)(9), 49,960 exome-sequenced individuals from the UK Biobank and over 4 million participants in the 23andMe genotyped dataset. After stringent variant curation, we identify 1,455 individuals with high-confidence pLoF variants in LRRK2. Experimental validation of three variants, combined with previous work(10), confirmed reduced protein levels in 82.5% of our cohort. We show that heterozygous pLoF variants in LRRK2 reduce LRRK2 protein levels but that these are not strongly associated with any specific phenotype or disease state. Our results demonstrate the value of large-scale genomic databases and phenotyping of human loss-of-function carriers for target validation in drug discovery.Peer reviewe