2,945 research outputs found
Non-equilibrium Dynamics of O(N) Nonlinear Sigma models: a Large-N approach
We study the time evolution of the mass gap of the O(N) non-linear sigma
model in 2+1 dimensions due to a time-dependent coupling in the large-
limit. Using the Schwinger-Keldysh approach, we derive a set of equations at
large which determine the time dependent gap in terms of the coupling.
These equations lead to a criterion for the breakdown of adiabaticity for slow
variation of the coupling leading to a Kibble-Zurek scaling law. We describe a
self-consistent numerical procedure to solve these large- equations and
provide explicit numerical solutions for a coupling which starts deep in the
gapped phase at early times and approaches the zero temperature equilibrium
critical point in a linear fashion. We demonstrate that for such a
protocol there is a value of the coupling where the gap
function vanishes, possibly indicating a dynamical instability. We study the
dependence of on both the rate of change of the coupling and
the initial temperature. We also verify, by studying the evolution of the mass
gap subsequent to a sudden change in , that the model does not display
thermalization within a finite time interval and discuss the implications
of this observation for its conjectured gravitational dual as a higher spin
theory in .Comment: 22 pages, 9 figures. Typos corrected, references rearranged and
added.v3 : sections rearranged, abstract modified, comment about Kibble-Zurek
scaling correcte
Adalimumab or Etanercept as first line biologic therapy in Enthesitis related arthritis (ERA) - a drug-survival single centre study spanning 10 years
Objectives: To analyse and compare drug-survival of adalimumab and etanercept (and their biosimilars) in biologic-naïve patients with ERA (Enthesitis-Related Arthritis). // Methods: In this retrospective observational study, conventional statistics and machine-learning were applied to compare drug-survival (adalimumab, etanercept and their biosimilars initiated: 2009–2019) in ERA and identify determinants. The primary outcome was discontinuation of treatment due to primary- or secondary-failure and adverse drug-reactions. // Results: During the observation period, 99 of 188 patients with ERA on first-line TNF inhibitors (etanercept-n=108, adalimumab-n=80) discontinued their treatment (median survival-time 3.9years, 95%CI 2.6-4.9years). Adalimumab was associated with longer drug-survival compared to etanercept especially after an initial positive response, with the median time to treatment discontinuation 4.9years (95% CI 3.9–5.7) for adalimumab, compared to 2years (95%CI 1.4–4.0) for etanercept (HR of treatment-discontinuation-0.49, 95%CI 0.32–-0.75, p=0.001). Adjusted by propensity-score, adalimumab-methotrexate combination was associated with longer drug survival, compared to adalimumab-monotherapy (HR-0.41, 95%CI 0.20–0.85), etanercept-monotherapy (HR-0.28, 95%CI 0.15–0.53), and etanercept-methotrexate combination (HR-0.39, 95%CI 0.21–0.73). The presence of HLA-B27 was associated with longer drug-survival (HR-0.50, 95%CI 0.29–0.87) following an initial positive response. Higher-CRP at baseline was associated with higher rate of primary-failure (HR-1.68, 95%CI 1.08–2.62). Axial-ERA (sacroiliitis±spinal-involvement) was associated with poorer drug-survival for both primary- and secondary-failure (overall HR-2.03, 95%CI 1.22–3.40). Adjusted by propensity-score, shorter drug-survival was observed in patients with baseline-CRP≥12.15 mg/L, but only in the context of axial-ERA, not in peripheral-ERA (no sacroiliitis/spinal-involvement) (HR-2.28, 95%CI 1.13–-3.64). // Conclusion: Following an initial positive primary response, continuing methotrexate with adalimumab was associated with the longest drug-survival compared to adalimumab-monotherapy or etanercept-based regimens. Axial-ERA was associated with a poorer drug-survival. A CRP >12.15 in patients with axial-ERA was associated with a higher rate of primary-failure. Further prospective studies are required to confirm these findings
Nonperturbative contributions to the quark form factor at high energy
The analysis of nonperturbative effects in high energy asymptotics of the
electomagnetic quark form factor is presented. It is shown that the
nonperturbative effects determine the initial value for the perturbative
evolution of the quark form factor and find their general structure with
respect to the high energy asymptotics. Within the Wilson integral formalism
which is natural for investigation of the soft, IR sensitive, part of the
factorized form factor, the structure of the instanton induced effects in the
evolution equation is discussed. It is demonstrated that the instanton
contributions result in the finite renormalization of the subleading
perturbative result and numerically are characterized by small factor
reflecting the diluteness of the QCD vacuum within the instanton liquid model.
The relevance of the IR renormalon induced effects in high energy asymptotic
behaviour is discussed. The consequences of the various analytization
procedures of the strong coupling constant in the IR domain are considered.Comment: REVTeX, 12 pages, 1 figure. Important references and discussions
added, misprints corrected, minor changes in tex
The use of happiness research for public policy
Research on happiness tends to follow a "benevolent dictator" approach where politicians pursue people's happiness. This paper takes an antithetic approach based on the insights of public choice theory. First, we inquire how the results of happiness research may be used to improve the choice of institutions. Second, we show that the policy approach matters for the choice of research questions and the kind of knowledge happiness research aims to provide. Third, we emphasize that there is no shortcut to an optimal policy maximizing some happiness indicator or social welfare function since governments have an incentive to manipulate this indicator
On soft singularities at three loops and beyond
We report on further progress in understanding soft singularities of massless
gauge theory scattering amplitudes. Recently, a set of equations was derived
based on Sudakov factorization, constraining the soft anomalous dimension
matrix of multi-leg scattering amplitudes to any loop order, and relating it to
the cusp anomalous dimension. The minimal solution to these equations was shown
to be a sum over color dipoles. Here we explore potential contributions to the
soft anomalous dimension that go beyond the sum-over-dipoles formula. Such
contributions are constrained by factorization and invariance under rescaling
of parton momenta to be functions of conformally invariant cross ratios.
Therefore, they must correlate the color and kinematic degrees of freedom of at
least four hard partons, corresponding to gluon webs that connect four eikonal
lines, which first appear at three loops. We analyze potential contributions,
combining all available constraints, including Bose symmetry, the expected
degree of transcendentality, and the singularity structure in the limit where
two hard partons become collinear. We find that if the kinematic dependence is
solely through products of logarithms of cross ratios, then at three loops
there is a unique function that is consistent with all available constraints.
If polylogarithms are allowed to appear as well, then at least two additional
structures are consistent with the available constraints.Comment: v2: revised version published in JHEP (minor corrections in Sec. 4;
added discussion in Sec. 5.3; refs. added); v3: minor corrections (eqs. 5.11,
5.12 and 5.29); 38 pages, 3 figure
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ERK1/2 signaling dominates over RhoA signaling in regulating early changes in RNA expression induced by endothelin-1 in neonatal rat cardiomyocytes
Cardiomyocyte hypertrophy is associated with changes in gene expression. Extracellular signal-regulated kinases 1/2 (ERK1/2) and RhoA [activated by hypertrophic agonists (e.g. endothelin-1)] regulate gene expression and are implicated in the response, but their relative significance in regulating the cardiomyocyte transcriptome is unknown. Our aim was to establish the significance of ERK1/2 and/or RhoA in the early cardiomyocyte transcriptomic response to endothelin-1.Cardiomyocytes were exposed to endothelin-1 (1 h) with/without PD184352 (to inhibit ERK1/2) or C3 transferase (C3T, to inhibit RhoA). RNA expression was analyzed using microarrays and qPCR. ERK1/2 signaling positively regulated approximately 65% of the early gene expression response to ET-1 with a small (approximately 2%) negative effect, whereas RhoA signaling positively regulated approximately 10% of the early gene expression response to ET-1 with a greater (approximately 14%) negative contribution. Of RNAs non-responsive to endothelin-1, 66 or 448 were regulated by PD184352 or C3T, respectively, indicating that RhoA had a more significant effect on baseline RNA expression. mRNAs upregulated by endothelin-1 encoded a number of receptor ligands (e.g. Ereg, Areg, Hbegf) and transcription factors (e.g. Abra/Srf) that potentially propagate the response.ERK1/2 dominates over RhoA in the early transcriptomic response to endothelin-1. RhoA plays a major role in maintaining baseline RNA expression but, with upregulation of Abra/Srf by endothelin-1, RhoA may regulate changes in RNA expression over longer times. Our data identify ERK1/2 as a more significant node than RhoA in regulating the early stages of cardiomyocyte hypertrophy
Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders
Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT
Altered growth characteristics of skin fibroblasts from wild-derived mice, and genetic loci regulating fibroblast clone size
Mouse fibroblast senescence in vitro is an important model for the study of aging at cellular level. However, common laboratory mouse strains may have lost some important allele variations related to aging processes. In this study, growth in vitro of tail skin fibroblasts (TSFs) derived from a wild-derived stock, Pohnpei (Pohn) mice, differed from growth of control C57BL/6 J (B6) TSFs. Pohn TSFs exhibited higher proliferative ability, fewer apoptotic cells, decreased expression of Cip1 , smaller surface areas, fewer cells positive for senescence associated-β-galactosidase (SA-β-gal) and greater resistance to H 2 O 2 -induced SA-β-gal staining and Cip1 expression. These data suggest that TSFs from Pohn mice resist cellular senescence-like changes. Using large clone ratio (LCR) as the phenotype, a quantitative trait locus (QTL) analysis in a Pohn/B6 backcross population found four QTLs for LCR: Fcs1 on Chr 3 at 55 cm; Fcs2 on Chr X at 50 cm; Fcs3 on Chr 4 at 51 cm and Fcs4 on Chr 10 at 25 cm. Together, these four QTLs explain 26.1% of the variations in LCRs in the N2 population. These are the first QTLs reported that regulate fibroblast growth. Glutathione S transferase mu ( GST-mu ) genes are overrepresented in the 95% confidence interval of Fcs1 , and Pohn TSFs have higher H 2 O 2 -induced GST-mu 4 , 5 and 7 mRNA levels than B6 TSFs. These enzymes may protect Pohn TSFs from oxidation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71416/1/j.1474-9726.2006.00208.x.pd
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