The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Guanfacine treatment improves ADHD phenotypes of impulsivity and hyperactivity in a neurofibromatosis type 1 mouse model

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a mutation in one copy of the neurofibromin gene (NF1+/-). Even though approximately 40-60% of children with NF1 meet the criteria for attention deficit hyperactivity disorder (ADHD), very few preclinical studies, if any, have investigated alterations in impulsivity and risk-taking behavior. Mice with deletion of a single NF1 gene (Nf1+/-) recapitulate many of the phenotypes of NF1 patients. METHODS: We compared wild-type (WT) and Nf1+/- mouse strains to investigate differences in impulsivity and hyperactivity using the delay discounting task (DDT), cliff avoidance reaction (CAR) test, and open field. We also investigated whether treatment with the clinically effective alpha-2A adrenergic receptor agonist, guanfacine (0.3 mg/kg, i.p.), would reverse deficits observed in behavioral inhibition. RESULTS: Nf1+/- mice chose a higher percentage of smaller rewards when both 10- and 20-s delays were administered compared to WT mice, suggesting Nf1+/- mice are more impulsive. When treated with guanfacine (0.3 mg/kg, i.p.), Nf1+/- mice exhibited decreased impulsive choice by waiting for the larger, delayed reward. Nf1+/- mice also exhibited deficits in behavioral inhibition compared to WT mice in the CAR test by repetitively entering the outer edge of the platform where they risk falling. Treatment with guanfacine ameliorated these deficits. In addition, Nf1+/- mice exhibited hyperactivity as increased distance was traveled compared to WT controls in the open field. This hyperactivity in Nf1+/- mice was reduced with guanfacine pre-treatment. CONCLUSIONS: Overall, our study confirms that Nf1+/- mice exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD, and can be used as a model system to identify alterations in neural circuitry associated with symptoms of ADHD in children with NF1

Pulmonary vasoconstrictor action of KCNQ potassium channel blockers

KCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+ currents mediated by KCNQ channels resemble a current underlying the resting K+ conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction. Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50 of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim

Nucleation in Systems with Elastic Forces

Systems with long-range interactions when quenced into a metastable state near the pseudo-spinodal exhibit nucleation processes that are quite different from the classical nucleation seen near the coexistence curve. In systems with long-range elastic forces the description of the nucleation process can be quite subtle due to the presence of bulk/interface elastic compatibility constraints. We analyze the nucleation process in a simple 2d model with elastic forces and show that the nucleation process generates critical droplets with a different structure than the stable phase. This has implications for nucleation in many crystal-crystal transitions and the structure of the final state

Hysteresis and hierarchies: dynamics of disorder-driven first-order phase transformations

We use the zero-temperature random-field Ising model to study hysteretic behavior at first-order phase transitions. Sweeping the external field through zero, the model exhibits hysteresis, the return-point memory effect, and avalanche fluctuations. There is a critical value of disorder at which a jump in the magnetization (corresponding to an infinite avalanche) first occurs. We study the universal behavior at this critical point using mean-field theory, and also present preliminary results of numerical simulations in three dimensions.Comment: 12 pages plus 2 appended figures, plain TeX, CU-MSC-747

Determination of Inflationary Observables by Cosmic Microwave Background Anisotropy Experiments

Inflation produces nearly Harrison-Zel'dovich scalar and tensor perturbation spectra which lead to anisotropy in the cosmic microwave background (CMB). The amplitudes and shapes of these spectra can be parametrized by $Q_S^2$, $r\equiv Q_T^2/Q_S^2$, $n_S$ and $n_T$ where $Q_S^2$ and $Q_T^2$ are the scalar and tensor contributions to the square of the CMB quadrupole and $n_S$ and $n_T$ are the power-lawspectral indices. Even if we restrict ourselves to information from angles greater than one third of a degree, three of these observables can be measured with some precision. The combination $130^{1-n_S}Q_S^2$ can be known to better than $\pm 0.3\%$. The scalar index $n_S$ can be determined to better than $\pm 0.02$. The ratio $r$ can be known to about $\pm 0.1$ for $n_S \simeq 1$ and slightly better for smaller $n_S$. The precision with which $n_T$ can be measured depends weakly on $n_S$ and strongly on $r$. For $n_S \simeq 1$ $n_T$ can be determined with a precision of about $\pm 0.056(1.5+r)/r$. A full-sky experiment with a $20'$beam using technology available today, similar to those being planned by several groups, can achieve the above precision. Good angular resolution is more important than high signal-to-noise ratio; for a given detector sensitivity and observing time a smaller beam provides significantly more information than a larger beam. The uncertainties in $n_S$ and $r$ are roughly proportional to the beam size. We briefly discuss the effects of uncertainty in the Hubble constant, baryon density, cosmological constant and ionization history.Comment: 28 pages of uuencoded postscript with 8 included figures. A postscript version is also available by anonymous ftp at ftp://astro.uchicago.edu/pub/astro/knox/fullsim.p

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Hysteresis, Avalanches, and Disorder Induced Critical Scaling: A Renormalization Group Approach

We study the zero temperature random field Ising model as a model for noise and avalanches in hysteretic systems. Tuning the amount of disorder in the system, we find an ordinary critical point with avalanches on all length scales. Using a mapping to the pure Ising model, we Borel sum the $6-\epsilon$ expansion to $O(\epsilon^5)$ for the correlation length exponent. We sketch a new method for directly calculating avalanche exponents, which we perform to $O(\epsilon)$. Numerical exponents in 3, 4, and 5 dimensions are in good agreement with the analytical predictions.Comment: 134 pages in REVTEX, plus 21 figures. The first two figures can be obtained from the references quoted in their respective figure captions, the remaining 19 figures are supplied separately in uuencoded forma

Global compactness results for nonlocal problems

International audienceWe obtain a Struwe type global compactness result for a class of nonlinear nonlocal problems involving the fractional $p-$Laplacian operator and nonlinearities at critical growth

Identifying house price diffusion patterns among Australian state capital cities

Prior research supports the proposition that house price diffusion shows a ripple effect along the spatial dimension. That is, house price changes in one region would reflect in subsequent house price changes in other regions, showing certain linkages among regions. Using the vector autoregression model and the impulse response function, this study investigates house price diffusion among Australia\u27s state capital cities, examining the response of one market to the innovation of other markets and determining the lagged terms for the maximum absolute value of the other markets\u27 responses. The results show that the most important subnational markets in Australia do not point to Sydney, rather towards Canberra and Hobart, while the Darwin market plays a role of buffer. The safest markets are Sydney and Melbourne. This study helps to predict house price movement trends in eight capital cities.<br /