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

Community-Based Participatory Research and Sustainability: The Petersburg Wellness Consortium

The principle and practice of sustainability is critical in community-based participatory research. Actively planning for and building community capacity to ensure sustainability is even more critical in research involving underserved populations and underrepresented minorities. The perception of researchers engaging with the community until their research needs have been met, then leaving the community with minimal, if any benefits, has all too often been the reality in these communities. This paper offers a case study of how an independent community consortium was borne from an academic/community research partnership in Petersburg, Virginia. We discuss lessons learned and practice implications as we describe the evolution of, and challenges associated with, cultivating a sustainable independent coalition

Rotational velocities of low-mass stars in the Pleiades and Hyades

We have obtained high-resolution spectra of 89 M dwarf members of the Pleiades and Hyades and have derived radial velocities, H-alpha equivalent widths, and spectroscopic rotational velocities for these stars. Typical masses of the newly-observed Pleiades and Hyades stars are ~ 0.4 M_{\sun} and ~ 0.2 M_{\sun}, respectively. We combine our new observations with previously published data to explore the rotational evolution of young stars with M < 0.4 M_\sun. The average rotation rate in the Hyades (age 600 Myr) is about 0.4 that of the Pleiades (110 Myr), and the mean equivalent widths of H-alpha are also lower. As found in previous studies, the correlation between rotation and chromospheric activity is identical in both clusters, implying that the lower activity in the Hyades is a result of the lower rotation rates. We show that a simple scaling of the Pleiades rotational distribution for M \leq 0.4 M_{\sun}, corrected for the effects of structural evolution, matches that of the Hyades if the average angular momentum loss from the Pleiades to the Hyades age is factor of \approx 6. This suggests that the distribution of initial angular momenta and disk-locking lifetimes for the lowest mass stars was similar in both clusters. We argue that this result provides further evidence for a saturation of the angular momentum loss rate at high rotational velocities.Comment: 22 pages, 11 figures, accepted for publication in The Astronomical Journal, tentatively scheduled for March 200

Rates of lobar atrophy in asymptomatic MAPT mutation carriers.

IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n&nbsp;=&nbsp;14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n&nbsp;=&nbsp;13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2&nbsp;years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers

Functional characterisation of a nicotinic acetylcholine receptor alpha subunit from the brown dog tick, Rhipicephalus sanguineus

Open Access funded by Biotechnology and Biological Sciences Research Council Under a Creative Commons license This work was supported by a Biotechnology and Biological Sciences Research Council (UK) Industrial CASE studentship award (BBSSM200411428) to K.L. with co-funding from Pfizer Animal Health, UK. We thank Dr. Andy Ball for help with rearing of ticks.Peer reviewedPublisher PD

Psychiatric intensive care units: A literature review

Background: Psychiatric Intensive Care Units (PICU) have been part of most inpatient psychiatric services for some time, however information about their functioning and outcome has not previously been collated. Aim: To conduct a systematic literature review to assess the current state of knowledge about such services. Method: A search of electronic databases was undertaken, followed by obtaining additional references from items obtained. Results: Over 50 papers in English containing some empirical data were identified. Most studies were retrospective. Typical PICU patients are: male; younger; single; unemployed; suffering from schizophrenia or mania; from a black Caribbean or African background; legally detained; with a forensic history. The most common reason for admission is for aggression management, and most patients stay a week or less. Evidence of the efficacy of PICU care is very poor. Conclusions: Most research so far has been small scale, and more substantial work using better methodologies is clearly required

Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study.

ObjectiveTo assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).MethodsPatients with Morquio A aged ≥5&nbsp;years (N = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0&nbsp;mg/kg/every other week (qow), elosulfase alfa 2.0&nbsp;mg/kg/week (weekly) or placebo for 24&nbsp;weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.ResultsAt week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95&nbsp;% CI 4.0, 40.9; P = 0.017) for weekly and 0.5 m (95&nbsp;% CI -17.8, 18.9; P = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95&nbsp;% CI -2.1, 4.4; P = 0.494) for weekly and -0.5 stairs/min (95&nbsp;% CI -3.7, 2.8; P = 0.778) for qow. Normalised urine KS was reduced at 24&nbsp;weeks in both regimens. In the weekly dose group, 22.4&nbsp;% of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3&nbsp;% of all infusions in this group) over 6&nbsp;months. No adverse events led to permanent treatment discontinuation.ConclusionsElosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile

The Problem of Hipparcos Distances to Open Clusters. II. Constraints from Nearby Field Stars

This paper examines the discrepancy between distances to nearby open clusters as determined by parallaxes from Hipparcos compared to traditional main sequence fitting. The biggest difference is seen for the Pleiades, and our hypothesis is that if the Hipparcos distance to the Pleiades is correct, then similar subluminous ZAMS stars should exist elsewhere, including the immediate solar neighborhood. We examine a color-magnitude diagram of very young and nearby solar-type stars and show that none of them lie below the traditional ZAMS, despite the fact that the Hipparcos Pleiades parallax would place its members 0.3 magnitude below that ZAMS. We also present analyses and observations of solar-type stars that do lie below the ZAMS and show that they are subluminous because of low metallicity and that they have the kinematics of old stars.Comment: 22 pages (including 4 tables) plus 6 figure

The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake

We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms

Evidence for Reflected Light from the Most Eccentric Exoplanet Known

This is an author-created, un-copyedited version of an article published in The Astrophysical Journal. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.3847/0004-637X/821/1/65.Planets in highly eccentric orbits form a class of objects not seen within our solar system. The most extreme case known among these objects is the planet orbiting HD20782, with an orbital period of 597days and an eccentricity of 0.96. Here we present new data and analysis for this system as part of the Transit Ephemeris Refinement and Monitoring Survey. We obtained CHIRON spectra to perform an independent estimation of the fundamental stellar parameters. New radial velocities from Anglo-Australian Telescope and PARAS observations during periastron passage greatly improve our knowledge of the eccentric nature of the orbit. The combined analysis of our Keplerian orbital and Hipparcos astrometry show that the inclination of the planetary orbit is >1.22, ruling out stellar masses for the companion. Our long-term robotic photometry show that the star is extremely stable over long timescales. Photometric monitoring of the star during predicted transit and periastron times using Microvariability and Oscillations of STars rule out a transit of the planet and reveal evidence of phase variations during periastron. These possible photometric phase variations may be caused by reflected light from the planet’s atmosphere and the dramatic change in star–planet separation surrounding the periastron passage.Peer reviewedFinal Accepted Versio