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Tess EK Cersonsky,1 Audra C Fain,2 Adam K Lewkowitz,3,4 Erika F Werner,5 Emily S Miller,3,4 Melissa A Clark,4,6 Nina K Ayala3,4 1Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Department of Obstetrics & Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 3Warren Alpert Medical School of Brown University, Providence, RI, USA; 4Department of Obstetrics & Gynecology, Women & Infants Hospital of Rhode Island, Providence, RI, USA; 5Department of Obstetrics & Gynecology, Tufts University School of Medicine, Boston, MA, USA; 6Department of Health Services, Policy and Practice, Brown School of Public Health, Providence, RI, USACorrespondence: Tess EK Cersonsky, Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine at Mount Sinai, 1176 5th Ave, 9th Floor, New York, NY, 10029, USA, Tel +1 203-828-7407, Email tess.cersonsky@gmail.comObjective: Outside of pregnancy, proactive coping has been associated with both mental and physical well-being and with improved quality of life in chronic disease, but its effects in pregnancy are understudied. Our objective was to evaluate whether early pregnancy proactive coping was associated with adverse perinatal outcomes.Study Design: This was a planned secondary analysis of nulliparous pregnant people recruited from a tertiary care center. Participants completed a validated assessment of proactive coping (Proactive Coping Scale) at 8– 20 weeks and were followed longitudinally through delivery. Detailed pregnancy and delivery data were collected by trained research personnel. The primary outcome was a composite of adverse perinatal outcomes including unplanned cesarean delivery, gestational diabetes, and hypertensive disorders of pregnancy. Secondary analyses included individual perinatal composite components and a neonatal morbidity composite measure. Multivariate regression compared adverse perinatal outcomes by Proactive Coping Scale quartile, controlling for a priori confounders.Results: Of the 281 parturients, the median Proactive Coping Scale score was 45.0 (range 25– 55), and 47% experienced an adverse perinatal outcome. After adjusting for confounders, those in the lowest Proactive Coping Scale quartile had 2.2 times higher odds of experiencing an adverse perinatal outcome compared to those in the highest Proactive Coping Scale quartile. There were no differences in odds of the individual composite components or the adverse neonatal outcome.Conclusion: Lower early pregnancy proactive coping scores are associated with significant increase in adverse perinatal outcomes. Interventions that target improving proactive coping may be a novel mechanism for reducing perinatal morbidity.Plain Language Summary: Proactive coping is the process of preparing for a stressor or goal, which has been studied in the context of chronic disease. We sought to understand how proactive coping relates to pregnancy outcomes. Our results indicated that higher proactive coping scores were associated with lower risk of adverse pregnancy outcomes. Therefore, interventions to increase proactive coping may have a role in reducing adverse pregnancy outcomes.Keywords: proactive coping, adverse pregnancy outcomes, cesarean delivery, gestational diabetes, hypertensive disorders of pregnancy

Mary Ann Clark,1 Francis G Duhay,2 Ann K Thompson,2 Michelle J Keyes,3 Lars G Svensson,4 Robert O Bonow,5 Benjamin T Stockwell,3 David J Cohen61The Neocure Group LLC, Washington, DC, 2Edwards Lifesciences Corporation, Irvine, CA, 3The Burgess Group LLC, Alexandria, VA, 4Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, OH, 5Center for Cardiovascular Innovation, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, 6Saint Luke's Mid America Heart Institute, Kansas City, MO, USABackground: Aortic valve replacement (AVR) is the standard of care for patients with severe, symptomatic aortic stenosis who are suitable surgical candidates, benefiting both non-high-risk and high-risk patients. The purpose of this study was to report long-term medical resource use and costs for patients following AVR and validate our assumption that high-risk patients have worse outcomes and are more costly than non-high-risk patients in this population.Methods: Patients with aortic stenosis who underwent AVR were identified in the 2003 Medicare 5% Standard Analytic Files and tracked over 5 years to measure clinical outcomes, medical resource use, and costs. An approximation to the logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) based on administrative data was used to assess surgical risk, with a computed logistic EuroSCORE > 20% considered high-risk.Results: We identified 1474 patients with aortic stenosis who underwent AVR, of whom 1222 (82.9%) were non-high-risk and 252 (17.1%) were high-risk. Among those who were non-high-risk, the mean age was 73.3 years, 464 (38.2%) were women, and the mean logistic EuroSCORE was 7%, whereas in those who were high-risk, the mean age was 77.6 years, 134 (52.8%) were women, and the mean logistic EuroSCORE was 37%. All-cause mortality was 33.2% for non-high-risk and 66.7% for high-risk patients at 5 years. Over this time period, non-high-risk patients experienced an average of 3.9 inpatient hospitalizations and total costs of $106,277 per patient versus 4.7 hospitalizations and total costs of $144,183 for high-risk patients.Conclusion: Among elderly patients undergoing AVR, long-term mortality and costs are substantially greater for high-risk than for non-high-risk individuals. These findings indicate that further research is needed to understand whether newer approaches to aortic valve replacement such as transcatheter AVR may be a lower cost, clinically valuable alternative.Keywords: aortic valve, replacement, health economics

The Deep Underground Neutrino Experiment (DUNE) is an upcoming neutrino oscillation experiment that is poised to answer key questions about the nature of neutrinos. Lattice QCD has the ability to make significant impact upon DUNE, beginning with computations of nucleon-neutrino interactions with weak currents. Nucleon amplitudes involving the axial form factor are part of the primary signal measurement process for DUNE, and precise calculations from LQCD can significantly reduce the uncertainty for inputs into Monte Carlo generators. Recent calculations of the nucleon axial charge have demonstrated that sub-percent precision is possible on this vital quantity. In these proceedings, we discuss preliminary results for the CalLat collaboration's calculation of the axial form factor of the nucleon. These computations are performed with Möbius domain wall valence quarks on HISQ sea quark ensembles generated by the MILC and CalLat collaborations. The results use a variety of ensembles including several at physical pion mass.

Lattice QCD calculations of two-nucleon interactions have been underway for about a decade, but still haven't reached the pion mass regime necessary for matching onto effective field theories and extrapolating to the physical point. Furthermore, results from different methods, including the use of the Lüscher formalism with different types of operators, as well as the HALQCD potential method, do not agree even qualitatively at very heavy pion mass. We investigate the role that different operators employed in the literature may play on the extraction of spectra for use within the Lüscher method. We first explore expectations from Effective Field Theory solved within a finite volume, for which the exact spectrum may be computed given different physical scenarios. We then present preliminary lattice QCD results for two-nucleon spectra calculated using different operators on a common lattice ensemble.

Excited state contamination remains one of the most challenging sources of systematic uncertainty to control in lattice QCD calculations of nucleon matrix elements and form factors: early time separations are contaminated by excited states and late times suffer from an exponentially bad signal-to-noise problem. High-statistics calculations at large time separations 1 fm are commonly used to combat these issues. In this work, focusing on gA, we explore the alternative strategy of utilizing a large number of relatively low-statistics calculations at short to medium time separations (0.2-1 fm), combined with a multistate analysis. On an ensemble with a pion mass of approximately 310 MeV and a lattice spacing of approximately 0.09 fm, we find this provides a more robust and economical method of quantifying and controlling the excited state systematic uncertainty. A quantitative separation of various types of excited states enables the identification of the transition matrix elements as the dominant contamination. The excited state contamination of the Feynman-Hellmann correlation function is found to reduce to the 1% level at approximately 1 fm while, for the more standard three-point functions, this does not occur until after 2 fm. Critical to our findings is the use of a global minimization, rather than fixing the spectrum from the two-point functions and using them as input to the three-point analysis. We find that the ground state parameters determined in such a global analysis are stable against variations in the excited state model, the number of excited states, and the truncation of early-time or late-time numerical data.

The Deep Underground Neutrino Experiment (DUNE) is an upcoming neutrinooscillation experiment that is poised to answer key questions about the natureof neutrinos. Lattice QCD has the ability to make significant impact upon DUNE,beginning with computations of nucleon-neutrino interactions with weakcurrents. Nucleon amplitudes involving the axial form factor are part of theprimary signal measurement process for DUNE, and precise calculations from LQCDcan significantly reduce the uncertainty for inputs into Monte Carlogenerators. Recent calculations of the nucleon axial charge have demonstratedthat sub-percent precision is possible on this vital quantity. In theseproceedings, we discuss preliminary results for the CalLat collaboration'scalculation of the axial form factor of the nucleon. These computations areperformed with M\"obius domain wall valence quarks on HISQ sea quark ensemblesgenerated by the MILC and CalLat collaborations. The results use a variety ofensembles including several at physical pion mass.

Excited state contamination remains one of the most challenging sources ofsystematic uncertainty to control in lattice QCD calculations of nucleon matrixelements and form factors: early time separations are contaminated by excitedstates and late times suffer from an exponentially bad signal-to-noise problem.High-statistics calculations at large time separations $\gtrsim1$ fm arecommonly used to combat these issues. In this work, focusing on $g_A$, weexplore the alternative strategy of utilizing a large number of relativelylow-statistics calculations at short to medium time separations (0.2--1 fm),combined with a multi-state analysis. On an ensemble with a pion mass ofapproximately 310 MeV and a lattice spacing of approximately 0.09 fm, we findthis provides a more robust and economical method of quantifying andcontrolling the excited state systematic uncertainty. A quantitative separationof various types of excited states enables the identification of the transitionmatrix elements as the dominant contamination. The excited state contaminationof the Feynman-Hellmann correlation function is found to reduce to the 1% levelat approximately 1 fm while for the more standard three-point functions, thisdoes not occur until after 2 fm. Critical to our findings is the use of aglobal minimization, rather than fixing the spectrum from the two-pointfunctions and using them as input to the three-point analysis. We find that theground state parameters determined in such a global analysis are stable againstvariations in the excited state model, the number of excited states, and thetruncation of early-time or late-time numerical data.

We report on a subpercent scale determination using the omega baryon mass and gradient-flow methods. The calculations are performed on 22 ensembles of Nf=2+1+1 highly improved, rooted staggered sea-quark configurations generated by the MILC and CalLat Collaborations. The valence quark action used is Möbius domain wall fermions solved on these configurations after a gradient-flow smearing is applied with a flowtime of tgf=1 in lattice units. The ensembles span four lattice spacings in the range 0.06a0.15 fm, six pion masses in the range 130mπ400 MeV and multiple lattice volumes. On each ensemble, the gradient-flow scales t0/a2 and w0/a and the omega baryon mass amω are computed. The dimensionless product of these quantities is then extrapolated to the continuum and infinite volume limits and interpolated to the physical light, strange and charm quark mass point in the isospin limit, resulting in the determination of t0=0.1422(14) fm and w0=0.1709(11) fm with all sources of statistical and systematic uncertainty accounted for. The dominant uncertainty in both results is the stochastic uncertainty, though for t0 there are comparable continuum extrapolation uncertainties. For w0, there is a clear path for a few-per-mille uncertainty just through improved stochastic precision, as recently obtained by the Budapest-Marseille-Wuppertal Collaboration.

We report on the first application of the stochastic Laplacian Heaviside method for computing multiparticle interactions with lattice QCD to the two-nucleon system. Like the Laplacian Heaviside method, this method allows for the construction of interpolating operators which can be used to construct a set of positive-definite two-nucleon correlation functions, unlike nearly all other applications of lattice QCD to two nucleons in the literature. It also allows for a variational analysis in which optimal linear combinations of the interpolating operators are formed that couple predominantly to the eigenstates of the system. Utilizing such methods has become of paramount importance to help resolve the discrepancy in the literature on whether two nucleons in either isospin channel form a bound state at pion masses heavier than physical, with the discrepancy persisting even in the SU(3)-flavor-symmetric point with all quark masses near the physical strange quark mass. This is the first in a series of papers aimed at resolving this discrepancy. In the present work, we employ the stochastic Laplacian Heaviside method without a hexaquark operator in the basis at a lattice spacing of a≈0.086 fm, lattice volume of L=48a≈4.1 fm and pion mass mπ≈714 MeV. With this setup, the observed spectrum of two-nucleon energy levels strongly disfavors the presence of a bound state in either the deuteron or dineutron channel.

We report on the first application of the stochastic Laplacian Heaviside method for computing multiparticle interactions with lattice QCD to the two-nucleon system. Like the Laplacian Heaviside method, this method allows for the construction of interpolating operators which can be used to construct a set of positive-definite two-nucleon correlation functions, unlike nearly all other applications of lattice QCD to two nucleons in the literature. It also allows for a variational analysis in which optimal linear combinations of the interpolating operators are formed that couple predominantly to the eigenstates of the system. Utilizing such methods has become of paramount importance to help resolve the discrepancy in the literature on whether two nucleons in either isospin channel form a bound state at pion masses heavier than physical, with the discrepancy persisting even in the SU(3)-flavor-symmetric point with all quark masses near the physical strange quark mass. This is the first in a series of papers aimed at resolving this discrepancy. In the present work, we employ the stochastic Laplacian Heaviside method without a hexaquark operator in the basis at a lattice spacing of a≈0.086 fm, lattice volume of L=48a≈4.1 fm and pion mass mπ≈714 MeV. With this setup, the observed spectrum of two-nucleon energy levels strongly disfavors the presence of a bound state in either the deuteron or dineutron channel.

We report the results of a lattice quantum chromodynamics calculation of FK/Fπ using Möbius domain-wall fermions computed on gradient-flowed Nf=2+1+1 highly improved staggered quark (HISQ) ensembles. The calculation is performed with five values of the pion mass ranging from 130 400 MeV, four lattice spacings of a∼0.15, 0.12, 0.09 and 0.06 fm and multiple values of the lattice volume. The interpolation/extrapolation to the physical pion and kaon mass point, the continuum, and infinite volume limits are performed with a variety of different extrapolation functions utilizing both the relevant mixed-action effective field theory expressions as well as discretization-enhanced continuum chiral perturbation theory formulas. We find that the a∼0.06 fm ensemble is helpful, but not necessary to achieve a subpercent determination of FK/Fπ. We also include an estimate of the strong isospin breaking corrections and arrive at a final result of FK+/Fπ+=1.1942(45) with all sources of statistical and systematic uncertainty included. This is consistent with the Flavour Lattice Averaging Group average value, providing an important benchmark for our lattice action. Combining our result with experimental measurements of the pion and kaon leptonic decays leads to a determination of |Vus|/|Vud|=0.2311(10).

Observation of neutrinoless double beta decay, a lepton number violating process that has been proposed to clarify the nature of neutrino masses, has spawned an enormous world-wide experimental effort. Relating nuclear decay rates to high-energy, beyond the standard model (BSM) physics requires detailed knowledge of nonperturbative QCD effects. Using lattice QCD, we compute the necessary matrix elements of short-range operators, which arise due to heavy BSM mediators, that contribute to this decay via the leading order π^{-}→π^{+} exchange diagrams. Utilizing our result and taking advantage of effective field theory methods will allow for model-independent calculations of the relevant two-nucleon decay, which may then be used as input for nuclear many-body calculations of the relevant experimental decays. Contributions from short-range operators may prove to be equally important to, or even more important than, those from long-range Majorana neutrino exchange.

The axial coupling of the nucleon, gA, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of gA makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome1,2: contamination of gA from excited states must be controlled in the calculations and statistical precision must be improved markedly2-10. Here we use an unconventional method 11 inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a gA value of 1.271 ± 0.013, which has a precision of about one per cent.

We report on salient features of a mixed lattice QCD action using valence Möbius domain-wall fermions solved on the dynamical Nf=2+1+1 highly improved staggered quark sea-quark ensembles generated by the MILC Collaboration. The approximate chiral symmetry properties of the valence fermions are shown to be significantly improved by utilizing the gradient-flow scheme to first smear the highly improved staggered quark configurations. The greater numerical cost of the Möbius domain-wall inversions is mitigated by the highly efficient QUDA library optimized for NVIDIA GPU accelerated compute nodes. We have created an interface to this optimized QUDA solver in Chroma. We provide tuned parameters of the action and performance of QUDA using ensembles with the lattice spacings a≃{0.15,0.12,0.09} fm and pion masses mπ≃{310,220,130} MeV. We have additionally generated two new ensembles with a∼0.12 fm and mπ∼{400,350} MeV. With a fixed flow time of tgf=1 in lattice units, the residual chiral symmetry breaking of the valence fermions is kept below 10% of the light quark mass on all ensembles, mres0.1×ml, with moderate values of the fifth dimension L5 and a domain-wall height M5≤1.3. As a benchmark calculation, we perform a continuum, infinite volume, physical pion and kaon mass extrapolation of FK±/Fπ± and demonstrate our results are independent of flow time and consistent with the FLAG determination of this quantity at the level of less than one standard deviation.

We report on a lattice QCD calculation of the nucleon axial charge, $g_A$,using M\"{o}bius Domain-Wall fermions solved on the dynamical $N_f=2+1+1$ HISQensembles after they are smeared using the gradient-flow algorithm. Thecalculation is performed with three pion masses, $m_\pi\sim\{310,220,130\}$MeV. Three lattice spacings ($a\sim\{0.15,0.12,0.09\}$ fm) are used with theheaviest pion mass, while the coarsest two spacings are used on the middle pionmass and only the coarsest spacing is used with the near physical pion mass. Onthe $m_\pi\sim220$ MeV, $a\sim0.12$ fm point, a dedicated volume study isperformed with $m_\pi L \sim \{3.22,4.29,5.36\}$. Using a new strategymotivated by the Feynman-Hellmann Theorem, we achieve a precise determinationof $g_A$ with relatively low statistics, and demonstrable control over theexcited state, continuum, infinite volume and chiral extrapolation systematicuncertainties, the latter of which remains the dominant uncertainty. Our finaldetermination at 2.6\% total uncertainty is $g_A = 1.278(21)(26)$, with thefirst uncertainty including statistical and systematic uncertainties fromfitting and the second including model selection systematics related to thechiral and continuum extrapolation. The largest reduction of the seconduncertainty will come from a greater number of pion mass points as well as moreprecise lattice QCD results near the physical pion mass.

This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had “in the pipeline” as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed.

Abstract 5‐Fluorouracil (5‐FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5‐FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5‐FU on post‐transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell‐cell communication. We found that treatment of colorectal cancer (CRC) cells with 5‐FU represses sEV export of miRNA and snRNA‐derived RNAs, but promotes export of snoRNA‐derived RNAs. Strikingly, 5‐FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5‐FU exposure led to increased levels of cellular small RNAs containing a variety of methyl‐modified bases. These unexpected findings show that 5‐FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs.

RESUMO A partir do enredo “Chico Buarque da Mangueira”, proposto por Alexandre Louzada para o Carnaval de 1998 da Estação Primeira de Mangueira, cujo desfile se sagrou campeão naquele ano, a proposta do trabalho é lançar luzes sobre a construção de um enredo biográfico e, mais além, sobre os processos de criação mais amplos que permeiam a realização carnavalesca de enredos e desfiles, bem como suas possibilidades educativas, tomadas em sentido amplo. Levando-se em conta, portanto, a construção do enredo de 1998, analisar-se-ão temas sobre a criação carnavalesca de histórias desfiladas na Sapucaí, articulando-se as mediações propostas pelas Escolas de Samba para carnavalizar um tema e apresentá-lo na Avenida, e suas ressonâncias como possibilidades pedagógicas, políticas e educativas.

Editors of several journals in the field of hydrology met during the General Assembly of the European Geosciences Union-EGU in Vienna in April 2017. This event was a follow-up of similar meetings held in 2013 and 2015. These meetings enable the group of editors to review the current status of the journals and the publication process, and to share thoughts on future strategies. Journals were represented at the 2017 meeting by their editors, as shown in the list of authors. The main points on invigorating hydrological research through journal publications are communicated in this joint editorial published in the above journals.