Association of BRAFV600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers

Background: Studies have demonstrated an association of the BRAFV600E mutation and microRNA (miR) expression with aggressive clinicopathologic features in papillary thyroid cancer (PTC). Analysis of BRAFV600E mutations with miR expression data may improve perioperative decision making for patients with PTC, specifically in identifying patients harboring central lymph node metastases (CLNM). Methods: Between January 2012 and June 2013, 237 consecutive patients underwent total thyroidectomy and prophylactic central lymph node dissection (CLND) at four endocrine surgery centers. All tumors were tested for the presence of the BRAFV600E mutation and miR-21, miR-146b-3p, miR-146b-5p, miR-204, miR-221, miR-222, and miR-375 expression. Bivariate and multivariable analyses were performed to examine associations between molecular markers and aggressive clinicopathologic features of PTC. Results: Multivariable logistic regression analysis of all clinicopathologic features found miR-146b-3p and miR-146b-5p to be independent predictors of CLNM, while the presence of BRAFV600E almost reached significance. Multivariable logistic regression analysis limited to only predictors available preoperatively (molecular markers, age, sex, and tumor size) found miR-146b-3p, miR-146b-5p, miR-222, and BRAFV600E mutation to predict CLNM independently. While BRAFV600E was found to be associated with CLNM (48% mutated in node-positive cases vs. 28% mutated in node-negative cases), its positive and negative predictive values (48% and 72%, respectively) limit its clinical utility as a stand-alone marker. In the subgroup analysis focusing on only classical variant of PTC cases (CVPTC), undergoing prophylactic lymph node dissection, multivariable logistic regression analysis found only miR-146b-5p and miR-222 to be independent predictors of CLNM, while BRAFV600E was not significantly associated with CLNM. Conclusion: In the patients undergoing prophylactic CLNDs, miR-146b-3p, miR-146b-5p, and miR-222 were found to be predictive of CLNM preoperatively. However, there was significant overlap in expression of these miRs in the two outcome groups. The BRAFV600E mutation, while being a marker of CLNM when considering only preoperative variables among all histological subtypes, is likely not a useful stand-alone marker clinically because the difference between node-positive and node-negative cases was small. Furthermore, it lost significance when examining only CVPTC. Overall, our results speak to the concept and interpretation of statistical significance versus actual applicability of molecular markers, raising questions about their clinical usefulness as individual prognostic markers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140269/1/thy.2015.0378.pd

A Comparison of Scent Marking between a Monogamous and Promiscuous Species of Peromyscus: Pair Bonded Males Do Not Advertise to Novel Females

Scent marking can provide behavioral and physiological information including territory ownership and mate advertisement. It is unknown how mating status and pair cohabitation influence marking by males from different social systems. We compared the highly territorial and monogamous California mouse (Peromyscus californicus) to the less territorial and promiscuous white-footed mouse (P. leucopus). Single and mated males of both species were assigned to one of the following arenas lined with filter paper: control (unscented arena), male scented (previously scent-marked by a male conspecific), or females present (containing females in small cages). As expected, the territorial P. californicus scent marked and overmarked an unfamiliar male conspecific's scent marks more frequently than P. leucopus. Species differences in responses to novel females were also found based on mating status. The presence of unfamiliar females failed to induce changes in scent marking in pair bonded P. californicus even though virgin males increased marking behavior. Pair bonding appears to reduce male advertisement for novel females. This is in contrast to P. leucopus males that continue to advertise regardless of mating status. Our data suggest that communication through scent-marking can diverge significantly between species based on mating system and that there are physiological mechanisms that can inhibit responsiveness of males to female cues

Measurements of double-helicity asymmetries in inclusive J/ψJ/\psi production in longitudinally polarized p+pp+p collisions at s=510\sqrt{s}=510 GeV

We report the double helicity asymmetry, $A_{LL}^{J/\psi}$, in inclusive $J/\psi$ production at forward rapidity as a function of transverse momentum $p_T$ and rapidity $|y|$. The data analyzed were taken during $\sqrt{s}=510$ GeV longitudinally polarized $p$$+$$p$ collisions at the Relativistic Heavy Ion Collider (RHIC) in the 2013 run using the PHENIX detector. At this collision energy, $J/\psi$ particles are predominantly produced through gluon-gluon scatterings, thus $A_{LL}^{J/\psi}$ is sensitive to the gluon polarization inside the proton. We measured $A_{LL}^{J/\psi}$ by detecting the decay daughter muon pairs $\mu^+ \mu^-$ within the PHENIX muon spectrometers in the rapidity range $1.2<|y|<2.2$. In this kinematic range, we measured the $A_{LL}^{J/\psi}$ to be $0.012 \pm 0.010$~(stat)~$\pm$~$0.003$(syst). The $A_{LL}^{J/\psi}$ can be expressed to be proportional to the product of the gluon polarization distributions at two distinct ranges of Bjorken $x$: one at moderate range $x \approx 0.05$ where recent RHIC data of jet and $\pi^0$ double helicity spin asymmetries have shown evidence for significant gluon polarization, and the other one covering the poorly known small-$x$ region $x \approx 2\times 10^{-3}$. Thus our new results could be used to further constrain the gluon polarization for $x< 0.05$.Comment: 335 authors, 10 pages, 4 figures, 3 tables, 2013 data. Version accepted for publication by Phys. Rev. D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Cross sections and double-helicity asymmetries of midrapidity inclusive charged hadrons in p+p collisions at sqrt(s)=62.4 GeV

Unpolarized cross sections and double-helicity asymmetries of single-inclusive positive and negative charged hadrons at midrapidity from p+p collisions at sqrt(s)=62.4 GeV are presented. The PHENIX measurements for 1.0 < p_T < 4.5 GeV/c are consistent with perturbative QCD calculations at next-to-leading order in the strong coupling constant, alpha_s. Resummed pQCD calculations including terms with next-to-leading-log accuracy, yielding reduced theoretical uncertainties, also agree with the data. The double-helicity asymmetry, sensitive at leading order to the gluon polarization in a momentum-fraction range of 0.05 ~< x_gluon ~< 0.2, is consistent with recent global parameterizations disfavoring large gluon polarization.Comment: PHENIX Collaboration. 447 authors, 12 pages, 5 figures, 5 tables. Submitted to Physical Review

Inclusive cross section and single-transverse-spin asymmetry for very forward neutron production in polarized p+p collisions at sqrt(s)=200 GeV

The energy dependence of the single-transverse-spin asymmetry, A_N, and the cross section for neutron production at very forward angles were measured in the PHENIX experiment at RHIC for polarized p+p collisions at sqrt(s)=200 GeV. The neutrons were observed in forward detectors covering an angular range of up to 2.2 mrad. We report results for neutrons with momentum fraction of x_F=0.45 to 1.0. The energy dependence of the measured cross sections were consistent with x_F scaling, compared to measurements by an ISR experiment which measured neutron production in unpolarized p+p collisions at sqrt(s)=30.6--62.7 GeV. The cross sections for large x_F neutron production for p+p collisions, as well as those in e+p collisions measured at HERA, are described by a pion exchange mechanism. The observed forward neutron asymmetries were large, reaching A_N=-0.08+/-0.02 for x_F=0.8; the measured backward asymmetries, for negative x_F, were consistent with zero. The observed asymmetry for forward neutron production is discussed within the pion exchange framework, with interference between the spin-flip amplitude due to the pion exchange and nonflip amplitudes from all Reggeon exchanges. Within the pion exchange description, the measured neutron asymmetry is sensitive to the contribution of other Reggeon exchanges even for small amplitudes.Comment: 383 authors, 16 pages, 18 figures, 6 tables. Submitted to Phys. Rev. D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Inclusive cross section and double helicity asymmetry for pi^0 production in p+p collisions at sqrt(s) = 62.4 GeV

The PHENIX experiment presents results from the RHIC 2006 run with polarized proton collisions at sqrt(s) = 62.4 GeV for inclusive pi^0 production at mid-rapidity. Unpolarized cross section results are measured for transverse momenta p_T = 0.5 to 7 GeV/c. Next-to-leading order perturbative quantum chromodynamics calculations are compared with the data, and while the calculations are consistent with the measurements, next-to-leading logarithmic corrections improve the agreement. Double helicity asymmetries A_LL are presented for p_T = 1 to 4 GeV/c and probe the higher range of Bjorken_x of the gluon (x_g) with better statistical precision than our previous measurements at sqrt(s)=200 GeV. These measurements are sensitive to the gluon polarization in the proton for 0.06 < x_g < 0.4.Comment: 387 authors from 63 institutions, 10 pages, 6 figures, 1 table. Submitted to Physical Review D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

J/psi suppression at forward rapidity in Au+Au collisions at sqrt(s_NN)=39 and 62.4 GeV

We present measurements of the J/psi invariant yields in sqrt(s_NN)=39 and 62.4 GeV Au+Au collisions at forward rapidity (1.2<|y|<2.2). Invariant yields are presented as a function of both collision centrality and transverse momentum. Nuclear modifications are obtained for central relative to peripheral Au+Au collisions (R_CP) and for various centrality selections in Au+Au relative to scaled p+p cross sections obtained from other measurements (R_AA). The observed suppression patterns at 39 and 62.4 GeV are quite similar to those previously measured at 200 GeV. This similar suppression presents a challenge to theoretical models that contain various competing mechanisms with different energy dependencies, some of which cause suppression and others enhancement.Comment: 365 authors, 10 pages, 11 figures, 4 tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Quadrupole Anisotropy in Dihadron Azimuthal Correlations in Central dd++Au Collisions at sNN\sqrt{s_{_{NN}}}=200 GeV

The PHENIX collaboration at the Relativistic Heavy Ion Collider (RHIC) reports measurements of azimuthal dihadron correlations near midrapidity in $d$$+$Au collisions at $\sqrt{s_{_{NN}}}$=200 GeV. These measurements complement recent analyses by experiments at the Large Hadron Collider (LHC) involving central $p$$+$Pb collisions at $\sqrt{s_{_{NN}}}$=5.02 TeV, which have indicated strong anisotropic long-range correlations in angular distributions of hadron pairs. The origin of these anisotropies is currently unknown. Various competing explanations include parton saturation and hydrodynamic flow. We observe qualitatively similar, but larger, anisotropies in $d$$+$Au collisions compared to those seen in $p$$+$Pb collisions at the LHC. The larger extracted $v_2$ values in $d$$+$Au collisions at RHIC are consistent with expectations from hydrodynamic calculations owing to the larger expected initial-state eccentricity compared with that from $p$$+$Pb collisions. When both are divided by an estimate of the initial-state eccentricity the scaled anisotropies follow a common trend with multiplicity that may extend to heavy ion data at RHIC and the LHC, where the anisotropies are widely thought to arise from hydrodynamic flow.Comment: 375 authors, 7 pages, 5 figures. Published in Phys. Rev. Lett. v2 has minor changes to text and figures in response to PRL referee suggestions. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm