Molecule Microscopy

Contains research objectives and reports on three research projects.Francis L. Friedman ChairNational Institutes of Health (Grant AM-31546

Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression

Two-year visual field outcomes of the treatment for advanced glaucoma study (TAGS)

PURPOSE: to compare visual field (VF) progression between the two arms of the Treatment of Advanced Glaucoma Study (TAGS) DESIGN: post-hoc analysis of VF data from a two-arm multicenter randomized controlled clinical trial METHODS: 453 patients with newly diagnosed advanced open-angle glaucoma in at least one eye from 27 centers in the United Kingdom were randomized to either trabeculectomy (N = 227) or medications in their index eye (N = 226) and followed-up for two years with two 24-2 VF tests at baseline, 4, 12 and 24 months. We analyzed data for participants with a reliable VF (False positive rate < 15%) at baseline and at least two other time-points. MAIN OUTCOME MEASURES: Average difference in rate of progression (RoP) was analyzed using a hierarchical Bayesian model. Time for each eye to progress from baseline beyond specific cut-offs (0.5, 1, 1.5 and 2 dB) was compared using survival analysis. RESULTS: 211 eyes in the trabeculectomy-first arm and 203 eyes in the medications-first arm were analyzed. The average RoPs (Estimate [95% Credible Intervals]) were -0.59 [-0.88, -0.31] dB/year in the medications-first arm and -0.40 [-0.67, -0.13] dB/year in the trabeculectomy-first arm. The difference was not significant (Bayesian p-value = 0.353). More eyes progressed in the medications-first arm: ≥0.5 dB (p = 0.001), ≥1dB (p = 0.014), ≥1.5dB (p = 0.071) and ≥2dB (p = 0.061). CONCLUSIONS: there was no significant difference in the average RoP at two years. Initial trabeculectomy significantly reduced the proportion of progressing eyes

Molecule Microscopy

Contains research objectives and reports on seven research projects.Whitaker Health Sciences FundFrancis L. Friedman ChairNational Institutes of Health (Grant AM-31546)National Institutes of Health (Grant AM-25535)International Business Machines, Inc

Molecular Physics

Contains report on one research project.International Business Machines, Inc.Francis L. Freidman Chai

Lithium in the Intermediate-Age Open Cluster, NGC 3680

High-dispersion spectra centered on the Li 6708 A line have been obtained for 70 potential members of the open cluster NGC 3680, with an emphasis on stars in the turnoff region. A measurable Li abundance has been derived for 53 stars, 39 of which have radial velocities and proper motions consistent with cluster membership. After being transferred to common temperature and abundance scales, previous Li estimates have been combined to generate a sample of 49 members, 40 of which bracket the cluster Li-dip. Spectroscopic elemental analysis of 8 giants and 5 turnoff stars produces [Fe/H] = -0.17 +/- 0.07 (sd) and -0.07 +/- 0.02 (sd), respectively. We also report measurements of Ca, Si and Ni which are consistent with scaled-solar ratios within the errors. Adopting [Fe/H] = -0.08 (Sect. 3.6), Y^2 isochrone comparisons lead to an age of 1.75 +/- 0.10 Gyr and an apparent modulus of (m-M) = 10.30 +/- 0.15 for the cluster, placing the center of the Li-dip at 1.35 +/- 0.03 solar masses. Among the giants, 5 of 9 cluster members are now known to have measurable Li with A(Li) near 1.0. A combined sample of dwarfs in the Hyades and Praesepe is used to delineate the Li-dip profile at 0.7 Gyr and [Fe/H] = +0.15, establishing its center at 1.42 +/- 0.02 solar masses and noting the possible existence of secondary dip on its red boundary. When evolved to the typical age of the clusters NGC 752, IC 4651 and NGC 3680, the Hyades/Praesepe Li-dip profile reproduces the observed morphology of the combined Li-dip within the CMD's of the intermediate-age clusters while implying a metallicity dependence for the central mass of the Li-dip given by Mass = (1.38 +/-0.04) + (0.4 +/- 0.2)[Fe/H]. The implications of the similarity of the Li-dichotomy among giants in NGC 752 and IC 4651 and the disagreement with the pattern among NGC 3680 giants are discussed.Comment: Latex ms. is 56 pages, including 10 figures and 4 tables. Accepted for the Astronomical Journa

Effect of the velopharynx on intraluminal pressures in reconstructed pharynges derived from individuals with and without sleep apnea

The most collapsible part of the upper airway in the majority of individuals is the velopharynx which is the segment positioned behind the soft palate. As such it is an important morphological region for consideration in elucidating the pathogenesis of obstructive sleep apnea (OSA). This study compared steady flow properties during inspiration in the pharynges of nine male subjects with OSA and nine body-mass index (BMI)- and age-matched control male subjects without OSA. The k–ωωSST turbulence model was used to simulate the flow field in subject-specific pharyngeal geometric models reconstructed from anatomical optical coherence tomography (aOCT) data. While analysis of the geometry of reconstructed pharynges revealed narrowing at velopharyngeal level in subjects with OSA, it was not possible to clearly distinguish them from subjects without OSA on the basis of pharyngeal size and shape alone. By contrast, flow simulations demonstrated that pressure fields within the narrowed airway segments were sensitive to small differences in geometry and could lead to significantly different intraluminal pressure characteristics between subjects. The ratio between velopharyngeal and total pharyngeal pressure drops emerged as a relevant flow-based criterion by which subjects with OSA could be differentiated from those without

Molecular Physics

Contains reports on two research projects.F.L. Freidman ChairNational Institutes of Health (Grant AM 25535)Whitaker FoundationInternational Business Machines, Inc

Molecule Microscopy

Contains research objectives and reports on four research projects.National Institutes of Health (Grant AM-25535)Whitaker FoundationFrancis L. Friedman Chai

WIYN Open Cluster Study. XXXIX. Abundances in NGC 6253 from HYDRA Spectroscopy of the Li 6708 A Region

High-dispersion spectra of 89 potential members of the old, super-metal-rich open cluster, NGC 6253, have been obtained with the HYDRA multi-object spectrograph. Based upon radial-velocity measurements alone, 47 stars at the turnoff of the cluster color-magnitude diagram (CMD) and 18 giants are identified as potential members. Five turnoff stars exhibit evidence of binarity while proper-motion data eliminates two of the dwarfs as members. The mean cluster radial velocity from probable single-star members is -29.4 +/- 1.3 km/sec (sd). A discussion of the current estimates for the cluster reddening, derived independently of potential issues with the BV cluster photometry, lead to an adopted reddening of E(B-V) = 0.22 +/- 0.04. From equivalent width analyses of 38 probable single-star members near the CMD turnoff, the weighted average abundances are found to be [Fe/H] = +0.43 +/- 0.01, [Ni/H] = +0.53 +/- 0.02 and [Si/H] = +0.43 (+0.03,-0.04), where the errors refer to the standard errors of the weighted mean. Weak evidence is found for a possible decline in metallicity with increasing luminosity among stars at the turnoff. We discuss the possibility that our turnoff stars have been affected by microscopic diffusion. For 15 probable single-star members among the giants, spectrum synthesis leads to abundances of +0.46 (+0.02,-0.03) for [Fe/H]. While less than half the age of NGC 6791, NGC 6253 is at least as metal-rich and, within the uncertainties, exhibits the same general abundance pattern as that typified by super-metal-rich dwarfs of the galactic bulge.Comment: 5 Tables, 9 figures, 45 page