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  • A new wave front shape-based approach for acoustic source localization in an anisotropic plate without knowing its material properties

    Sen, Novonil; Kundu, Tribikram; Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, AZ 85721, USA; Department of Civil Engineering and Engineering Mechanics, University of Arizona, Tucson, AZ 85721, USA (ELSEVIER SCIENCE BV, 2018-07)
    Estimating the location of an acoustic source in a structure is an important step towards passive structural health monitoring. Techniques for localizing an acoustic source in isotropic structures are well developed in the literature. Development of similar techniques for anisotropic structures, however, has gained attention only in the recent years and has a scope of further improvement. Most of the existing techniques for anisotropic structures either assume a straight line wave propagation path between the source and an ultrasonic sensor or require the material properties to be known. This study considers different shapes of the wave front generated during an acoustic event and develops a methodology to localize the acoustic source in an anisotropic plate from those wave front shapes. An elliptical wave front shape-based technique was developed first, followed by the development of a parametric curve-based technique for non-elliptical wave front shapes. The source coordinates are obtained by minimizing an objective function. The proposed methodology does not assume a straight line wave propagation path and can predict the source location without any knowledge of the elastic properties of the material. A numerical study presented here illustrates how the proposed methodology can accurately estimate the source coordinates. (C) 2018 Elsevier B.V. All rights reserved.
  • Action of automorphisms on irreducible characters of symplectic groups

    Taylor, Jay; Univ Arizona, Dept Math, 617 N Santa Rita Ave, Tucson, AZ 85721 USA (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018-07-01)
    Assume G is a finite symplectic group Sp(2n)(q) over a finite field F-q of odd characteristic. We describe the action of the automorphism group Aut(G) on the set Irr(G) of ordinary irreducible characters of G. This description relies on the equivariance of Deligne-Lusztig induction with respect to automorphisms. We state a version of this equivariance which gives a precise way to compute the automorphism on the corresponding Levi subgroup; this may be of independent interest. As an application we prove that the global condition in Spath's criterion for the inductive McKay condition holds for the irreducible characters of Sp(2n)(q). (C) 2018 Elsevier Inc. All rights reserved.
  • An ecohydrological stream type classification of intermittent and ephemeral streams in the southwestern United States

    Levick, Lainie; Hammer, Samantha; Lyon, Russell; Murray, Joel; Birtwistle, Amy; Guertin, Phillip; Goodrich, David; Bledsoe, Brian; Laituri, Melinda; Univ Arizona (ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2018-08)
    An ecohydrological stream type classification was developed to improve decision making for ephemeral and intermittent streams at four military reservations in the southwestern U.S.: Fort Irwin, Yuma Proving Ground (YPG), Fort Huachuca, and Fort Bliss. Agglomerative hierarchical cluster analysis was used to classify stream reaches by ecohydrologic properties (vegetation, hydrologic, and geomorphic attributes derived using geographic information system analyses), and Classification and Regression Trees (CART) were used to determine thresholds for each variable for a predictive model. Final stream types were determined from statistical analyses, cluster validity tests, examination of mapped clusters, and site knowledge. Climate regime and geomorphology were most important for YPG and Fort Irwin where annual precipitation is low. Vegetation variables were important at Fort Bliss and hydrologic variables were important at Fort Huachuca where higher annual precipitation and a bimodal rainfall pattern occur. The classification results and input variables are spatially linked to specific stream reaches, allowing managers to identify locations with similar attributes to support management actions. These methods enable the development of a stream type classification in gauged or ungauged watersheds and for areas where intensive field data collection is not feasible.
  • An age-dependent vocal tract model for males and females based on anatomic measurements

    Story, Brad H.; Vorperian, Houri K.; Bunton, Kate; Durtschi, Reid B.; Univ Arizona, Speech Language & Hearing Sci (ACOUSTICAL SOC AMER AMER INST PHYSICS, 2018-05)
    The purpose of this study was to take a first step toward constructing a developmental and sex-specific version of a parametric vocal tract area function model representative of male and female vocal tracts ranging in age from infancy to 12 yrs, as well as adults. Anatomic measurements collected from a large imaging database of male and female children and adults provided the dataset from which length warping and cross-dimension scaling functions were derived, and applied to the adult-based vocal tract model to project it backward along an age continuum. The resulting model was assessed qualitatively by projecting hypothetical vocal tract shapes onto midsagittal images from the cohort of children, and quantitatively by comparison of formant frequencies produced by the model to those reported in the literature. An additional validation of modeled vocal tract shapes was made possible by comparison to cross-sectional area measurements obtained for children and adults using acoustic pharyngometry. This initial attempt to generate a sex-specific developmental vocal tract model paves a path to study the relation of vocal tract dimensions to documented prepubertal acoustic differences. (C) 2018 Acoustical Society of America.
  • The 4-Celled Tetrabaena socialis Nuclear Genome Reveals the Essential Components for Genetic Control of Cell Number at the Origin of Multicellularity in the Volvocine Lineage

    Featherston, Jonathan; Arakaki, Yoko; Hanschen, Erik R; Ferris, Patrick J; Michod, Richard E; Olson, Bradley J S C; Nozaki, Hisayoshi; Durand, Pierre M; Univ Arizona, Dept Ecol & Evolutionary Biol (OXFORD UNIV PRESS, 2018-04)
    Multicellularity is the premier example of a major evolutionary transition in individuality and was a foundational event in the evolution of macroscopic biodiversity. The volvocine chlorophyte lineage is well suited for studying this process. Extant members span unicellular, simple colonial, and obligate multicellular taxa with germ-soma differentiation. Here, we report the nuclear genome sequence of one of the most morphologically simple organisms in this lineage-the 4-celled colonial Tetrabaena socialis and compare this to the three other complete volvocine nuclear genomes. Using conservative estimates of gene family expansions a minimal set of expanded gene families was identified that associate with the origin of multicellularity. These families are rich in genes related to developmental processes. A subset of these families is lineage specific, which suggests that at a genomic level the evolution of multicellularity also includes lineagespecific molecular developments. Multiple points of evidence associate modifications to the ubiquitin proteasomal pathway (UPP) with the beginning of coloniality. Genes undergoing positive or accelerating selection in the multicellular volvocines were found to be enriched in components of the UPP and gene families gained at the origin of multicellularity include components of the UPP. A defining feature of colonial/multicellular life cycles is the genetic control of cell number. The genomic data presented here, which includes diversification of cell cycle genes and modifications to the UPP, align the genetic components with the evolution of this trait.
  • Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism

    Jeong, Mark Y.; Lin, Ying H.; Wennersten, Sara A.; Demos-Davies, Kimberly M.; Cavasin, Maria A.; Mahaffey, Jennifer H.; Monzani, Valmen; Saripalli, Chandrasekhar; Mascagni, Paolo; Reece, T. Brett; Ambardekar, Amrut V.; Granzier, Henk L.; Dinarello, Charles A.; McKinsey, Timothy A.; Univ Arizona, Dept Cellular & Mol Med; Univ Arizona, Sarver Mol Cardiovasc Res Program (AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-07)
    There are no approved drugs for the treatment of heart failure with preserved ejection fraction (HFpEF), which is characterized by left ventricular (LV) diastolic dysfunction. We demonstrate that ITF2357 (givinostat), a clinical-stage inhibitor of histone deacetylase (HDAC) catalytic activity, is efficacious in two distinct murine models of diastolic dysfunction with preserved EF. ITF2357 blocked LV diastolic dysfunction due to hypertension in Dahl salt-sensitive (DSS) rats and suppressed aging-induced diastolic dysfunction in normotensive mice. HDAC inhibitor-mediated efficacy was not due to lowering blood pressure or inhibiting cellular and molecular events commonly associated with diastolic dysfunction, including cardiac fibrosis, cardiac hypertrophy, or changes in cardiac titin and myosin isoform expression. Instead, ex vivo studies revealed impairment of cardiac myofibril relaxation as a previously unrecognized, myocyte-autonomous mechanism for diastolic dysfunction, which can be ameliorated by HDAC inhibition. Translating these findings to humans, cardiac myofibrils from patients with diastolic dysfunction and preserved EF also exhibited compromised relaxation. These data suggest that agents such as HDAC inhibitors, which potentiate cardiac myofibril relaxation, hold promise for the treatment of HFpEF in humans.
  • The Statistical Properties of Solar Wind Temperature Parameters Near 1 au

    Wilson III, Lynn B.; Stevens, Michael L.; Kasper, Justin C.; Klein, Kristopher G.; Maruca, Bennett A.; Bale, Stuart D.; Bowen, Trevor A.; Pulupa, Marc P.; Salem, Chadi S.; Univ Arizona, Lunar & Planetary Lab (IOP Publishing, 2018-06-01)
  • Majority of Solar Wind Intervals Support Ion-Driven Instabilities

    Klein, K. G.; Alterman, B. L.; Stevens, M. L.; Vech, D.; Kasper, J. C.; Univ Arizona, Lunar & Planetary Lab (American Physical Society, 2018-05-18)
    We perform a statistical assessment of solar wind stability at 1 AU against ion sources of free energy using Nyquist’s instability criterion. In contrast to typically employed threshold models which consider a single free-energy source, this method includes the effects of proton and He2+ temperature anisotropy with respect to the background magnetic field as well as relative drifts between the proton core, proton beam, and He2+ components on stability. Of 309 randomly selected spectra from the Wind spacecraft, 53.7% are unstable when the ion components are modeled as drifting bi-Maxwellians; only 4.5% of the spectra are unstable to long-wavelength instabilities. A majority of the instabilities occur for spectra where a proton beam is resolved. Nearly all observed instabilities have growth rates γ slower than instrumental and ion-kinetic-scale timescales. Unstable spectra are associated with relatively large He2+ drift speeds and/or a departure of the core proton temperature from isotropy; other parametric dependencies of unstable spectra are also identified.
  • Nature of Stochastic Ion Heating in the Solar Wind: Testing the Dependence on Plasma Beta and Turbulence Amplitude

    Vech, Daniel; Klein, Kristopher G.; Kasper, Justin C.; Univ Arizona, Lunar & Planetary Lab (IOP Publishing, 2017-11-16)
  • A Zone of Preferential Ion Heating Extends Tens of Solar Radii from the Sun

    Kasper, J. C.; Klein, K. G.; Weber, T.; Maksimovic, M.; Zaslavsky, A.; Bale, S. D.; Maruca, B. A.; Stevens, M. L.; Case, A. W.; Univ Arizona, Lunar & Planetary Lab (IOP Publishing, 2017-11-07)
    The extreme temperatures and nonthermal nature of the solar corona and solar wind arise from an unidentified physical mechanism that preferentially heats certain ion species relative to others. Spectroscopic indicators of unequal temperatures commence within a fraction of a solar radius above the surface of the Sun, but the outer reach of this mechanism has yet to be determined. Here we present an empirical procedure for combining interplanetary solar wind measurements and a modeled energy equation including Coulomb relaxation to solve for the typical outer boundary of this zone of preferential heating. Applied to two decades of observations by the Wind spacecraft, our results are consistent with preferential heating being active in a zone extending from the transition region in the lower corona to an outer boundary 20–40 solar radii from the Sun, producing a steady-state super-massproportional α-to-proton temperature ratio of 5.2–5.3. Preferential ion heating continues far beyond the transition region and is important for the evolution of both the outer corona and the solar wind. The outer boundary of this zone is well below the orbits of spacecraft at 1 au and even closer missions such as Helios and MESSENGER, meaning it is likely that no existing mission has directly observed intense preferential heating, just residual signatures. We predict that the Parker Solar Probe will be the first spacecraft with a perihelion sufficiently close to the Sun to pass through the outer boundary, enter the zone of preferential heating, and directly observe the physical mechanism in action.
  • Magnetic Reconnection May Control the Ion-scale Spectral Break of Solar Wind Turbulence

    Vech, Daniel; Mallet, Alfred; Klein, Kristopher G.; Kasper, Justin C.; Univ Arizona, Lunar & Planetary Lab (IOP Publishing, 2018-03-15)
    The power spectral density of magnetic fluctuations in the solar wind exhibits several power-law-like frequency ranges with a well-defined break between approximately 0.1 and 1 Hz in the spacecraft frame. The exact dependence of this break scale on solar wind parameters has been extensively studied but is not yet fully understood. Recent studies have suggested that reconnection may induce a break in the spectrum at a “disruption scale” lD, which may be larger than the fundamental ion kinetic scales, producing an unusually steep spectrum just below the break. We present a statistical investigation of the dependence of the break scale on the proton gyroradius ρi, ion inertial length di, ion sound radius ρs, proton–cyclotron resonance scale ρc, and disruption scale lD as a function of b^i. We find that the steepest spectral indices of the dissipation range occur when βe is in the range of 0.1–1 and the break scale is only slightly larger than the ion sound scale (a situation occurring 41% of the time at 1 au), in qualitative agreement with the reconnection model. In this range, the break scale shows a remarkably good correlation with lD. Our findings suggest that, at least at low βe, reconnection may play an important role in the development of the dissipation range turbulent cascade and cause unusually steep (steeper than −3) spectral indices.
  • Astrophysical gyrokinetics: turbulence in pressure-anisotropic plasmas at ion scales and beyond

    Kunz, M. W.; Abel, I. G.; Klein, K. G.; Schekochihin, A. A.; Univ Arizona, Lunar & Planetary Lab (CAMBRIDGE UNIV PRESS, 2018-04)
    We present a theoretical framework for describing electromagnetic kinetic turbulence in a multi-species, magnetized, pressure-anisotropic plasma. The turbulent fluctuations are assumed to be small compared to the mean field, to be spatially anisotropic with respect to it and to have frequencies small compared to the ion cyclotron frequency. At scales above the ion-Larmor radius, the theory reduces to the pressure-anisotropic generalization of kinetic reduced magnetohydrodynamics (KRMHD) formulated by Kunz et al. (J. Plasma Phys., vol. 81, 2015, 325810501). At scales at and below the ion-Larmor radius, three main objectives are achieved. First, we analyse the linear response of the pressure-anisotropic gyrokinetic system, and show it to be a generalization of previously explored limits. The effects of pressure anisotropy on the stability and collisionless damping of Alfvenic and compressive fluctuations are highlighted, with attention paid to the spectral location and width of the frequency jump that occurs as Alfven waves transition into kinetic Alfven waves. Secondly, we derive and discuss a very general gyrokinetic free-energy conservation law, which captures both the KRMHD free-energy conservation at long wavelengths and dual cascades of kinetic Alfven waves and ion entropy at sub-ion-Larmor scales. We show that non-Maxwellian features in the distribution function change the amount of phase mixing and the efficiency of magnetic stresses, and thus influence the partitioning of free energy amongst the cascade channels. Thirdly, a simple model is used to show that pressure anisotropy, even within the bounds imposed on it by firehose and mirror instabilities, can cause order-of-magnitude variations in the ion-to-electron heating ratio due to the dissipation of Alfvenic turbulence. Our theory provides a foundation for determining how pressure anisotropy affects turbulent fluctuation spectra, the differential heating of particle species and the ratio of parallel and perpendicular phase mixing in space and astrophysical plasmas.
  • Signal Processing and Coding Techniques for 2-D Magnetic Recording: An Overview

    Garani, Shayan Srinivasa; Dolecek, Lara; Barry, John; Sala, Frederic; Vasic, Bane; Univ Arizona, Dept Elect & Comp Engn (IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2018-02)
    Two-dimensional magnetic recording (TDMR) is an emerging storage technology that aims to achieve areal densities on the order of 10 Tb/in 2, mainly driven by innovative channels engineering with minimal changes to existing head/ media designs within a systems framework. Significant additive areal density gains can be achieved by using TDMR over bit patterned media (BPM) and energy-assisted magnetic recording (EAMR). In TDMR, the sectors are inherently 2-D with reduced track pitch and bit widths, leading to severe 2-D intersymbol interference (ISI). This necessitates the development of powerful 2-D signal processing and coding algorithms for mitigating 2-D ISI, timing artifacts, jitter, and electronics noise resulting from irregular media grain positions and read-head electronics. The algorithms have to be eventually realized within a read/write channel architecture as a part of a system-on-chip (SoC) within the disk controller system. In this work, we provide a wide overview of TDMR technology, channel models and capacity, signal processing algorithms (detection and timing recovery), and error-correcting codes attuned to 2-D channels. The innovations and advances described not only make TDMR a promising future technology, but may serve a broader engineering audience as well.
  • Hard-Decision Decoding of LDPC Codes Under Timing Errors: Overview and New Results

    Brkic, Srdan; Ivanis, Predrag; Vasic, Bane; Univ Arizona, Dept Elect & Comp Engn (IEEE, 2017)
    This paper contains a survey on iterative decoders of low-density parity-check (LDPC) codes built form unreliable logic gates. We assume that hardware unreliability comes from supply voltage reduction, which causes probabilistic gate failures, called timing errors. We are able to demonstrate robustness of simple Gallager B decoder to timing errors, when applied on codes free of small trapping sets, as well as positive effects that timing errors have on the decoding of codes with contain small trapping sets. Furthermore, we show that concept of guaranteed error correction can be applied to the decoders made partially from unreliable components. In contrast to the decoding under uncorrelated gate failures, we prove that bit-flipping decoding under timing errors can achieve arbitrary low error probability. Consequently, we formulate condition sufficient that memory architecture, which employs bit-flipping decoder, preserved all stored information.
  • 2-D LDPC Codes and Joint Detection and Decoding for Two-Dimensional Magnetic Recording

    Matcha, Chaitanya Kumar; Roy, Shounak; Bahrami, Mohsen; Vasic, Bane; Srinivasa, Shayan Garani; Univ Arizona, Dept Elect & Comp Engn (IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2018-02)
    Two-dimensional magnetic recording (TDMR) is a promising technology for boosting areal densities (ADs) using sophisticated signal processing algorithms within a systems framework. The read/write channel architectures have to effectively tackle 2-D inter-symbol interference (ISI), 2-D synchronization errors, media and electronic noise sources, as well as thermal asperities resulting in burst erasures. The 1-D low-density parity check (LDPC) codes are well studied to correct large 1-D burst errors/erasures. However, such 1-D LDPC codes are not suitable for correcting 2-D burst errors/erasures due to the 2-D span of errors. In this paper, we propose construction of a native 2-D LDPC code to effectively correct 2-D burst erasures. We also propose a joint detection and decoding engine based on the generalized belief propagation algorithm to simultaneously handle 2-D ISI, as well as correct bit/burst errors for TDMR channels. This paper is novel in two aspects: 1) we propose the construction of native 2-D LDPC codes to correct large 2-D burst erasures and 2) we develop a 2-D joint signal detection-decoder engine that incorporates 2-D ISI constraints, and modulation code constrains along with LDPC decoding. The native 2-D LDPC code can correct >20% more burst erasures compared with the 1-D LDPC code over a 128 x 256 2-D page of detected bits. Also, the proposed algorithm is observed to achieve a signal-to-noise ratio gain of >0.5 dB in bit error rate performance (translating to 10% increase in ADs around the 1.8 Tb/in(2) regime with grain sizes of 9 nm) as compared with a decoupled detector-decoder system configuration over a small 2-D LDPC code of size 16 x 16. The efficacy of our proposed algorithm and system architecture is evaluated by assessing AD gains via simulations for a TDMR configuration comprising of a 2-D generalized partial response over the Voronoi media model assuming perfect 2-D synchronization.
  • Serial Concatenation of Reed Muller and LDPC Codes with Low Error Floor

    Xiao, Xin; Nasseri, Mona; Vasic, Bane; Lin, Shu; Univ Arizona, Dept Elect & Comp Engn (IEEE, 2017)
    In this paper, we propose a concatenated coding scheme involving an outer Reed-Muller (RM) code and an inner Finite Field low-density parity check (LDPC) code of medium length and high rate. It lowers the error floor of inner Finite Field LDPC code. This concatenation scheme offers flexibility in design and it is easy to implement. In addition, the decoding works in a serial turbo manner and has no harmful trapping sets of size smaller than the minimum distance of the outer code. The simulation results indicate that the proposed serial concatenation can eliminate the dominant trapping sets of the inner Finite Field LDPC code.
  • African Americans Are Less Likely to Receive Care by a Cardiologist During an Intensive Care Unit Admission for Heart Failure.

    Breathett, Khadijah; Liu, Wenhui G; Allen, Larry A; Daugherty, Stacie L; Blair, Irene V; Jones, Jacqueline; Grunwald, Gary K; Moss, Marc; Kiser, Tyree H; Burnham, Ellen; Vandivier, R William; Clark, Brendan J; Lewis, Eldrin F; Mazimba, Sula; Battaglia, Catherine; Ho, P Michael; Peterson, Pamela N; Univ Arizona, Sarver Heart Ctr, Div Cardiovasc Med (ELSEVIER SCI LTD, 2018-05-01)
    This study sought to determine whether the likelihood of receiving primary intensive care unit (ICU) care by a cardiologist versus a noncardiologist was greater for Caucasians than for African Americans admitted to an ICU for heart failure (HF). The authors further evaluated whether primary ICU care by a cardiologist is associated with higher in-hospital survival, irrespective of race. Increasing data demonstrate an association between better HF outcomes and care by a cardiologist. It is unclear if previously noted racial differences in cardiology care persist in an ICU setting. Using the Premier database, adult patients admitted to an ICU with a primary discharge diagnosis of HF from 2010 to 2014 were included. Hierarchical logistic regression models were used to determine the association between race and primary ICU care by a cardiologist, adjusting for patient and hospital variables. Cox regression with inverse probability weighting was used to assess the association between cardiology care and in-hospital mortality. Among 104,835 patients (80.3% Caucasians, 19.7% African Americans), Caucasians had higher odds of care by a cardiologist than African Americans (adjusted odds ratio: 1.42; 95% confidence interval: 1.34 to 1.51). Compared with a noncardiologist, primary ICU care by a cardiologist was associated with higher in-hospital survival (adjusted hazard ratio: 1.20, 95% confidence interval: 1.11 to 1.28). The higher likelihood of survival did not differ by patient race (interaction p = 0.32).
  • Trends in Early Prenatal Care Among Women with Pre-Existing Diabetes: Have Income Disparities Changed?

    Breathett, Khadijah; Filley, Jessica; Pandey, Madhaba; Rai, Nayanjot; Peterson, Pamela N.; Univ Arizona, Sarver Heart Ctr, Div Cardiol (MARY ANN LIEBERT, INC, 2018-01)
    Background: Women with pre-existing diabetes are at high maternal risk for comorbidities and death, particularly when early prenatal care is not received. Low income is a known barrier to early prenatal care. It is unknown whether recent policies to expand access to prenatal care have reduced income disparities. We hypothesized that income disparities would be minimized and that the odds of receipt of first trimester prenatal care among women with pre-existing diabetes would become similar across income strata over time. Material and Methods: Using the Colorado birth certificate registry from 2007 to 2014, receipt of prenatal care was assessed retrospectively in 2,497 women with pre-existing diabetes. Logistic regression was used to examine the association between high (>$50,000), medium ($25,000-50,000), and low (<$25,000) income strata and receipt of first trimester prenatal care by birth year, adjusted for demographics. Results: High, medium, and low income represented 29.5%, 19.0%, and 51.5% of the cohort, respectively. Women with high income were more likely to receive first trimester care than women with low income from 2007 [adjusted odds ratio, 95% confidence interval: 2.16 (1.18, 3.96)] through 2013 [1.66 (1.01, 2.73)], but significant differences were no longer observed in 2014 [1.59 (0.89, 2.84)]. The likelihood of receiving first trimester prenatal care was not significantly different between medium- and low-income strata from 2007 [1.07 (0.66, 1.74)] through 2014 [0.77 (0.48, 1.23)]. Conclusions: From 2007 to 2013, women in Colorado with diabetes were more likely to receive early prenatal care if they were in the highest income stratum than in the lowest stratum. In 2014, receipt of first trimester care became equitable across all income strata. Future work should examine national patterns of income with receipt of prenatal care and outcomes among women with pre-existing diabetes.
  • Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial.

    Brilakis, Emmanouil S; Edson, Robert; Bhatt, Deepak L; Goldman, Steven; Holmes, David R; Rao, Sunil V; Shunk, Kendrick; Rangan, Bavana V; Mavromatis, Kreton; Ramanathan, Kodangudi; Bavry, Anthony A; Garcia, Santiago; Latif, Faisal; Armstrong, Ehrin; Jneid, Hani; Conner, Todd A; Wagner, Todd; Karacsonyi, Judit; Uyeda, Lauren; Ventura, Beverly; Alsleben, Aaron; Lu, Ying; Shih, Mei-Chiung; Banerjee, Subhash; Univ Arizona, Sarver Heart Ctr (ELSEVIER SCIENCE INC, 2018-05-19)
    Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions. Patients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50-99% stenosis of a 2·25-4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices. Enrolled patients were randomly assigned, in a 1:1 ratio, by phone randomisation system to receive a DES or BMS. Randomisation was stratified by presence or absence of diabetes and number of target SVG lesions requiring percutaneous coronary intervention (one or two or more) within each participating site by use of an adaptive scheme intended to balance the two stent type groups on marginal totals for the stratification factors. Patients, referring physicians, study coordinators, and outcome assessors were masked to group allocation. The primary endpoint was the 12-month incidence of target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularisation. The DIVA trial is registered with ClinicalTrials.gov, number NCT01121224. Between Jan 1, 2012, and Dec 31, 2015, 599 patients were randomly assigned to the stent groups, and the data for 597 patients were used. The patients' mean age was 68·6 (SD 7·6) years, and 595 (>99%) patients were men. The two stent groups were similar for most baseline characteristics. At 12 months, the incidence of target vessel failure was 17% (51 of 292) in the DES group versus 19% (58 of 305) in the BMS group (adjusted hazard ratio 0·92, 95% CI 0·63-1·34, p=0·70). Between-group differences in the components of the primary endpoint, serious adverse events, or stent thrombosis were not significant. Enrolment was stopped before the revised target sample size of 762 patients was reached. In patients undergoing stenting of de-novo SVG lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found. The study results have important economic implications in countries with high DES prices such as the USA, because they suggest that the lower-cost BMS can be used in SVG lesions without compromising either safety or efficacy.
  • Sensitive and specific post-call filtering of genetic variants in xenograft and primary tumors

    Mannakee, Brian K; Balaji, Uthra; Witkiewicz, Agnieszka K; Gutenkunst, Ryan N; Knudsen, Erik S; Univ Arizona, Dept Epidemiol & Biostat, Mel & Enid Zuckerman Coll Publ Hlth; Univ Arizona, Ctr Canc; Univ Arizona, Dept Med; Univ Arizona, Dept Pathol; Univ Arizona, Dept Mol & Cellular Biol (OXFORD UNIV PRESS, 2018-05-15)
    Motivation: Tumor genome sequencing offers great promise for guiding research and therapy, but spurious variant calls can arise from multiple sources. Mouse contamination can generate many spurious calls when sequencing patient-derived xenografts. Paralogous genome sequences can also generate spurious calls when sequencing any tumor. We developed a BLAST-based algorithm, Mouse And Paralog EXterminator (MAPEX), to identify and filter out spurious calls from both these sources. Results: When calling variants from xenografts, MAPEX has similar sensitivity and specificity to more complex algorithms. When applied to any tumor, MAPEX also automatically flags calls that potentially arise from paralogous sequences. Our implementation, mapexr, runs quickly and easily on a desktop computer. MAPEX is thus a useful addition to almost any pipeline for calling genetic variants in tumors.

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