Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies.

Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event

Does stress perfusion imaging improve the diagnostic accuracy of late gadolinium enhanced cardiac magnetic resonance for establishing the etiology of heart failure?

Background Late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) has excellent specificity, sensitivity and diagnostic accuracy for differentiating between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NICM). CMR first-pass myocardial perfusion imaging (perfusion-CMR) may also play role in distinguishing heart failure of ischemic and non-ischemic origins, although the utility of additional of stress perfusion imaging in such patients is unclear. The aim of this retrospective study was to assess whether the addition of adenosine stress perfusion imaging to LGE-CMR is of incremental value for differentiating ICM and NICM in patients with severe left ventricular systolic dysfunction (LVSD) of uncertain etiology. Methods We retrospectively identified 100 consecutive adult patients (median age 69 years (IQR 59–73)) with severe LVSD (mean LV EF 26.6 ± 7.0%) referred for perfusion-CMR to establish the underlying etiology of heart failure. The cause of heart failure was first determined on examination of CMR cine and LGE images in isolation. Subsequent examination of complete adenosine stress perfusion-CMR studies (cine, LGE and perfusion images) was performed to identify whether this altered the initial diagnosis. Results On LGE-CMR, 38 patients were diagnosed with ICM, 46 with NICM and 16 with dual pathology. With perfusion-CMR, there were 39 ICM, 44 NICM and 17 dual pathology diagnoses. There was excellent agreement in diagnoses between LGE-CMR and perfusion-CMR (κ 0.968, p<0.001). The addition of adenosine stress perfusion images to LGE-CMR altered the diagnosis in only two of the 100 patients. Conclusion The addition of adenosine stress perfusion-CMR to cine and LGE-CMR provides minimal incremental diagnostic yield for determining the etiology of heart failure in patients with severe LVSD

Simultaneous normal form transformation and model-order reduction for systems of coupled nonlinear oscillators

In this paper, we describe a direct normal form decomposition for systems of coupled nonlinear oscillators. We demonstrate how the order of the system can be reduced during this type of normal form transformation process. Two specific examples are considered to demonstrate particular challenges that can occur in this type of analysis. The first is a 2 d.f. system with both quadratic and cubic nonlinearities, where there is no internal resonance, but the nonlinear terms are not necessarily ε1-order small. To obtain an accurate solution, the direct normal form expansion is extended to ε2-order to capture the nonlinear dynamic behaviour, while simultaneously reducing the order of the system from 2 to 1 d.f. The second example is a thin plate with nonlinearities that are ε1-order small, but with an internal resonance in the set of ordinary differential equations used to model the low-frequency vibration response of the system. In this case, we show how a direct normal form transformation can be applied to further reduce the order of the system while simultaneously obtaining the normal form, which is used as a model for the internal resonance. The results are verified by comparison with numerically computed results using a continuation software

Ultraviolet asymptotics of scalar and pseudoscalar correlators in hot Yang-Mills theory

Inspired by recent lattice measurements, we determine the short-distance (a > omega >> pi T) asymptotics of scalar (trace anomaly) and pseudoscalar (topological charge density) correlators at 2-loop order in hot Yang-Mills theory. The results are expressed in the form of an Operator Product Expansion. We confirm and refine the determination of a number of Wilson coefficients; however some discrepancies with recent literature are detected as well, and employing the correct values might help, on the qualitative level, to understand some of the features observed in the lattice measurements. On the other hand, the Wilson coefficients show slow convergence and it appears uncertain whether this approach can lead to quantitative comparisons with lattice data. Nevertheless, as we outline, our general results might serve as theoretical starting points for a number of perhaps phenomenologically more successful lines of investigation.Comment: 27 pages. v2: minor improvements, published versio

Inductively guided circuits for ultracold dressed atoms

Recent progress in optics, atomic physics and material science has paved the way to study quantum effects in ultracold atomic alkali gases confined to non-trivial geometries. Multiply connected traps for cold atoms can be prepared by combining inhomogeneous distributions of DC and radio-frequency electromagnetic fields with optical fields that require complex systems for frequency control and stabilization. Here we propose a flexible and robust scheme that creates closed quasi-one-dimensional guides for ultracold atoms through the ‘dressing’ of hyperfine sublevels of the atomic ground state, where the dressing field is spatially modulated by inductive effects over a micro-engineered conducting loop. Remarkably, for commonly used atomic species (for example, 7Li and 87Rb), the guide operation relies entirely on controlling static and low-frequency fields in the regimes of radio-frequency and microwave frequencies. This novel trapping scheme can be implemented with current technology for micro-fabrication and electronic control

Three-loop HTL QCD thermodynamics

The hard-thermal-loop perturbation theory (HTLpt) framework is used to calculate the thermodynamic functions of a quark-gluon plasma to three-loop order. This is the highest order accessible by finite temperature perturbation theory applied to a non-Abelian gauge theory before the high-temperature infrared catastrophe. All ultraviolet divergences are eliminated by renormalization of the vacuum, the HTL mass parameters, and the strong coupling constant. After choosing a prescription for the mass parameters, the three-loop results for the pressure and trace anomaly are found to be in very good agreement with recent lattice data down to $T \sim 2-3\,T_c$, which are temperatures accessible by current and forthcoming heavy-ion collision experiments.Comment: 27 pages, 11 figures; corresponds with published version in JHE

Gauge invariant definition of the jet quenching parameter

In the framework of Soft-Collinear Effective Theory, the jet quenching parameter, $\hat{q}$, has been evaluated by adding the effect of Glauber gluon interactions to the propagation of a highly-energetic collinear parton in a medium. The result, which holds in covariant gauges, has been expressed in terms of the expectation value of two Wilson lines stretching along the direction of the four-momentum of the parton. In this paper, we show how that expression can be generalized to an arbitrary gauge by the addition of transverse Wilson lines. The transverse Wilson lines are explicitly computed by resumming interactions of the parton with Glauber gluons that appear only in non-covariant gauges. As an application of our result, we discuss the contribution to $\hat{q}$ coming from transverse momenta of order $g^2T$ in a medium that is a weakly-coupled quark-gluon plasma.Comment: 31 pages, 7 figures; journal versio