The clinical pharmacology of intranasal l-methamphetamine.

BackgroundWe studied the pharmacology of l-methamphetamine, the less abused isomer, when used as a nasal decongestant.Methods12 subjects self-administered l-methamphetamine from a nonprescription inhaler at the recommended dose (16 inhalations over 6 hours) then at 2 and 4 (32 and 64 inhalations) times this dose. In a separate session intravenous phenylephrine (200 microg) and l-methamphetamine (5 mg) were given to define alpha agonist pharmacology and bioavailability. Physiological, cardiovascular, pharmacokinetic, and subjective effects were measured.ResultsPlasma l-methamphetamine levels were often below the level of quantification so bioavailability was estimated by comparing urinary excretion of the intravenous and inhaled doses, yielding delivered dose estimates of 74.0 +/- 56.1, 124.7 +/- 106.6, and 268.1 +/- 220.5 microg for ascending exposures (mean 4.2 +/- 3.3 microg/inhalation). Physiological changes were minimal and not dose-dependent. Small decreases in stroke volume and cardiac output suggesting mild cardiodepression were seen.ConclusionInhaled l-methamphetamine delivered from a non-prescription product produced minimal effects but may be a cardiodepressant

Bayesian modelling of clusters of galaxies from multi-frequency pointed Sunyaev--Zel'dovich observations

We present a Bayesian approach to modelling galaxy clusters using multi-frequency pointed observations from telescopes that exploit the Sunyaev--Zel'dovich effect. We use the recently developed MultiNest technique (Feroz, Hobson & Bridges, 2008) to explore the high-dimensional parameter spaces and also to calculate the Bayesian evidence. This permits robust parameter estimation as well as model comparison. Tests on simulated Arcminute Microkelvin Imager observations of a cluster, in the presence of primary CMB signal, radio point sources (detected as well as an unresolved background) and receiver noise, show that our algorithm is able to analyse jointly the data from six frequency channels, sample the posterior space of the model and calculate the Bayesian evidence very efficiently on a single processor. We also illustrate the robustness of our detection process by applying it to a field with radio sources and primordial CMB but no cluster, and show that indeed no cluster is identified. The extension of our methodology to the detection and modelling of multiple clusters in multi-frequency SZ survey data will be described in a future work.Comment: 12 pages, 7 figures, submitted to MNRA

A parametric physical model for the intracluster medium and its use in joint SZ/X-ray analyses of galaxy clusters

We present a parameterized model of the intra-cluster medium that is suitable for jointly analysing pointed observations of the Sunyaev-Zel'dovich (SZ) effect and X-ray emission in galaxy clusters. The model is based on assumptions of hydrostatic equilibrium, the Navarro, Frenk and White (NFW) model for the dark matter, and a softened power law profile for the gas entropy. We test this entropy-based model against high and low signal-to-noise mock observations of a relaxed and recently-merged cluster from N-body/hydrodynamic simulations, using Bayesian hyper-parameters to optimise the relative statistical weighting of the mock SZ and X-ray data. We find that it accurately reproduces both the global values of the cluster temperature, total mass and gas mass fraction (fgas), as well as the radial dependencies of these quantities outside of the core (r > kpc). For reference we also provide a comparison with results from the single isothermal beta model. We confirm previous results that the single isothermal beta model can result in significant biases in derived cluster properties.Comment: Published in MNRAS. 20 pages. 9 figure

Presynaptic partner selection during retinal circuit reassembly varies with timing of neuronal regeneration in vivo

Whether neurons can restore their original connectivity patterns during circuit repair is unclear. Taking advantage of the regenerative capacity of zebrafish retina, we show here the remarkable specificity by which surviving neurons reassemble their connectivity upon regeneration of their major input. H3 horizontal cells (HCs) normally avoid red and green cones, and prefer ultraviolet over blue cones. Upon ablation of the major (ultraviolet) input, H3 HCs do not immediately increase connectivity with other cone types. Instead, H3 dendrites retract and re-extend to contact new ultraviolet cones. But, if regeneration is delayed or absent, blue-cone synaptogenesis increases and ectopic synapses are made with red and green cones. Thus, cues directing synapse specificity can be maintained following input loss, but only within a limited time period. Further, we postulate that signals from the major input that shape the H3 HC's wiring pattern during development persist to restrict miswiring after damage

Optimization of a high work function solution processed vanadium oxide hole-extracting layer for small molecule and polymer organic photovoltaic cells

We report a method of fabricating a high work function, solution processable vanadium oxide (V2Ox(sol)) hole-extracting layer. The atmospheric processing conditions of film preparation have a critical influence on the electronic structure and stoichiometry of the V2Ox(sol), with a direct impact on organic photovoltaic (OPV) cell performance. Combined Kelvin probe (KP) and ultraviolet photoemission spectroscopy (UPS) measurements reveal a high work function, n-type character for the thin films, analogous to previously reported thermally evaporated transition metal oxides. Additional states within the band gap of V2Ox(sol) are observed in the UPS spectra and are demonstrated using X-ray photoelectron spectroscopy (XPS) to be due to the substoichiometric nature of V2Ox(sol). The optimized V2Ox(sol) layer performance is compared directly to bare indium–tin oxide (ITO), poly(ethyleneoxythiophene):poly(styrenesulfonate) (PEDOT:PSS), and thermally evaporated molybdenum oxide (MoOx) interfaces in both small molecule/fullerene and polymer/fullerene structures. OPV cells incorporating V2Ox(sol) are reported to achieve favorable initial cell performance and cell stability attributes

High Electron Mobility in Vacuum and Ambient for PDIF-CN2 Single-Crystal Transistors

We have investigated the electron mobility on field-effect transistors based on PDIF-CN$_{2}$ single crystals. The family of the small molecules PDI8-CN$_{2}$ has been chosen for the promising results obtained for vapour-deposited thin film FETs. We used as gate dielectric a layer of PMMA (spinned on top of the SiO$_{2}$), to reduce the possibility of electron trapping by hydroxyl groups present at surface of the oxide. For these devices we obtained a room temperature mobility of 6 cm$^{2}$/Vs in vacuum and 3 cm$^{2}$/Vs in air. Our measurements demonstrate the possibility to obtain n-type OFETs with performances comparable to those of p-type devices.Comment: published online in JAC