Desynchronization of pathological low-frequency brain activity by the hypnotic drug zolpidem.

Reports of the beneficial effects of the hypnotic imidazopyridine, zolpidem, described in persistent vegetative state^1, 2^ have been replicated recently in brain-injured and cognitively impaired patients^3-7^. Previous single photon emission computed tomography (SPECT) studies have suggested that sub-sedative doses of zolpidem increased regional cerebral perfusion in affected areas^5, 8^, implying enhanced neuronal metabolic activity; which has led to speculation that zolpidem 'reawakens' functionally dormant cortex. However, a neuronal mechanism by which this hypnotic drug affords benefits to brain injured patients has yet to be demonstrated. Here, we report the action of sub-sedative doses of zolpidem on neuronal network oscillatory activity in human brain, measured using pharmaco-magnetoencephalography (pharmaco-MEG). Study participant JP suffered a stroke in 1996, causing major damage to the left hemisphere that impaired aspects of both motor and cognitive function. Pharmaco-MEG analyses revealed robust and persistent pathological theta (4-10Hz) and beta (15-30Hz) oscillations within the lesion penumbra and surrounding cortex. Administration of zolpidem (5mg) reduced the power of pathological theta and beta oscillations in all regions of the lesioned hemisphere. This desynchronizing effect correlated well with zolpidem uptake (occurring approximately 40 minutes after acute administration) and was coincident with marked improvements in cognitive and motor function. Control experiments revealed no effect of placebo, while a structurally unrelated hypnotic, zopiclone, administered at a comparable dose (3.5mg) elicited widespread increases in cortical oscillatory power in the beta (15-30Hz) band without functional improvement. These results suggest that in JP, specific motor and cognitive impairments are related to increased low-frequency oscillatory neuronal network activity. Zolpidem is unique amongst hypnotic drugs in its ability to desynchronize such pathological low-frequency activity, thereby restoring cognitive function

Detailed Chemical Abundances in NGC 5824: Another Metal-Poor Globular Cluster with Internal Heavy Element Abundance Variations

We present radial velocities, stellar parameters, and detailed abundances of 39 elements derived from high-resolution spectroscopic observations of red giant stars in the luminous, metal-poor globular cluster NGC 5824. We observe 26 stars in NGC 5824 using the Michigan/Magellan Fiber System (M2FS) and two stars using the Magellan Inamori Kyocera Echelle (MIKE) spectrograph. We derive a mean metallicity of [Fe/H]=-1.94+/-0.02 (statistical) +/-0.10 (systematic). The metallicity dispersion of this sample of stars, 0.08 dex, is in agreement with previous work and does not exceed the expected observational errors. Previous work suggested an internal metallicity spread only when fainter samples of stars were considered, so we cannot exclude the possibility of an intrinsic metallicity dispersion in NGC 5824. The M2FS spectra reveal a large internal dispersion in [Mg/Fe], 0.28 dex, which is found in a few other luminous, metal-poor clusters. [Mg/Fe] is correlated with [O/Fe] and anti-correlated with [Na/Fe] and [Al/Fe]. There is no evidence for internal dispersion among the other alpha- or Fe-group abundance ratios. Twenty-five of the 26 stars exhibit a n-capture enrichment pattern dominated by r-process nucleosynthesis ([Eu/Fe]=+0.11+/-0.12; [Ba/Eu]=-0.66+/-0.05). Only one star shows evidence of substantial s-process enhancement ([Ba/Fe]=+0.56+/-0.12; [Ba/Eu]=+0.38+/-0.14), but this star does not exhibit other characteristics associated with s-process enhancement via mass-transfer from a binary companion. The Pb and other heavy elements produced by the s-process suggest a timescale of no more than a few hundred Myr for star formation and chemical enrichment, like the complex globular clusters M2, M22, and NGC 5286.Comment: Accepted for publication in MNRAS. (26 pages, 18 figures, 9 tables including online data

A Search for Stars of Very Low Metal Abundance. VI. Detailed Abundances of 313 Metal-Poor Stars

We present radial velocities, equivalent widths, model atmosphere parameters, and abundances or upper limits for 53 species of 48 elements derived from high resolution optical spectroscopy of 313 metal-poor stars. A majority of these stars were selected from the metal-poor candidates of the HK Survey of Beers, Preston, and Shectman. We derive detailed abundances for 61% of these stars for the first time. Spectra were obtained during a 10-year observing campaign using the Magellan Inamori Kyocera Echelle spectrograph on the Magellan Telescopes at Las Campanas Observatory, the Robert G. Tull Coude Spectrograph on the Harlan J. Smith Telescope at McDonald Observatory, and the High Resolution Spectrograph on the Hobby-Eberly Telescope at McDonald Observatory. We perform a standard LTE abundance analysis using MARCS model atmospheres, and we apply line-by-line statistical corrections to minimize systematic abundance differences arising when different sets of lines are available for analysis. We identify several abundance correlations with effective temperature. A comparison with previous abundance analyses reveals significant differences in stellar parameters, which we investigate in detail. Our metallicities are, on average, lower by approx. 0.25 dex for red giants and approx. 0.04 dex for subgiants. Our sample contains 19 stars with [Fe/H] < -3.5, 84 stars with [Fe/H] < -3.0, and 210 stars with [Fe/H] < -2.5. Detailed abundances are presented here or elsewhere for 91% of the 209 stars with [Fe/H] < -2.5 as estimated from medium resolution spectroscopy by Beers, Preston, and Shectman. We will discuss the interpretation of these abundances in subsequent papers.Comment: Accepted for publication in the Astronomical Journal. 60 pages, 59 figures, 18 tables. Machine-readable versions of the long tables can be found in the ancillary data file

Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function:a randomised controlled trial

Background: Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance. Methods: We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of &lt;400 m and no contraindications to magnetic resonance imaging scanning. Outcomes were measured at baseline and 20 weeks. The primary outcome was post-exercise phosphocreatine (PCr) recovery rate measured using 31P magnetic resonance spectroscopy of the calf. Secondary outcomes included 6-min walk distance, short physical performance battery (SPPB), lean body mass measured by bioimpedance, endothelial function and quality of life. Results: In total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, −0.07 to 0.27], P = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4–46, P = 0.02]). This was more pronounced in those with high baseline oxidative stress and urate. Conclusion: Allopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress. </p

Detailed Chemical Abundances in the r-Process-Rich Ultra-Faint Dwarf Galaxy Reticulum 2

The ultra-faint dwarf galaxy Reticulum 2 (Ret 2) was recently discovered in images obtained by the Dark Energy Survey. We have observed the four brightest red giants in Ret 2 at high spectral resolution using the Michigan/Magellan Fiber System. We present detailed abundances for as many as 20 elements per star, including 12 elements heavier than the Fe group. We confirm previous detection of high levels of r-process material in Ret 2 (mean [Eu/Fe]=+1.69+/-0.05) found in three of these stars (mean [Fe/H]=-2.88+/-0.10). The abundances closely match the r-process pattern found in the well-studied metal-poor halo star CS22892-052. Such r-process-enhanced stars have not been found in any other ultra-faint dwarf galaxy, though their existence has been predicted by at least one model. The fourth star in Ret 2 ([Fe/H]=-3.42+/-0.20) contains only trace amounts of Sr ([Sr/Fe]=-1.73+/-0.43) and no detectable heavier elements. One r-process enhanced star is also enhanced in C (natal [C/Fe]=+1.1). This is only the third such star known, which suggests that the nucleosynthesis sites leading to C and r-process enhancements are decoupled. The r-process-deficient star is enhanced in Mg ([Mg/Fe]=+0.81+/-0.14), and the other three stars show normal levels of alpha-enhancement (mean [Mg/Fe]=+0.34+/-0.03). The abundances of other alpha and Fe-group elements closely resemble those in ultra-faint dwarf galaxies and metal-poor halo stars, suggesting that the nucleosynthesis that led to the large r-process enhancements either produced no light elements or produced light-element abundance signatures indistinguishable from normal supernovae.Comment: Accepted for publication in the Astronomical Journal. 12 pages, 6 figures, 8 table

Search for nearby Earth analogs I. 15 planet candidates found in PFS data

30 pages, 20 figures, 3 tables, accepted for publication in ApJSThe radial velocity (RV) method plays a major role in the discovery of nearby exoplanets. To efficiently find planet candidates from the data obtained in high-precision RV surveys, we apply a signal diagnostic framework to detect RV signals that are statistically significant, consistent in time, robust in the choice of noise models, and do not correlated with stellar activity. Based on the application of this approach to the survey data of the Planet Finder Spectrograph, we report 15 planet candidates located in 14 stellar systems. We find that the orbits of the planet candidates around HD 210193, 103949, 8326, and 71135 are consistent with temperate zones around these stars (where liquid water could exist on the surface). With periods of 7.76 and 15.14 days, respectively, the planet candidates around star HIP 54373 form a 1:2 resonance system. These discoveries demonstrate the feasibility of automated detection of exoplanets from large RV surveys, which may provide a complete sample of nearby Earth analogs.Peer reviewedFinal Accepted Versio