Residential treatment for combat-related posttraumatic stress disorder: Identifying trajectories of change and predictors of treatment response

Background Combat-related posttraumatic stress disorder (PTSD) can be a difficult condition to treat and has been associated with serious medical and economic issues among U.S. military veterans. Distinguishing between treatment responders vs. non-responders in this population has become an important public health priority. This study was conducted to identify pre-treatment characteristics of U.S. veterans with combat-related PTSD that might contribute to favorable and unfavorable responses to high value treatments for this condition. Method This study focused on 805 patients who completed a VHA PTSD residential program between 2000 and 2007. These patients completed the PTSD Clinical Checklist at pre-treatment, post-treatment, and a four-month follow-up assessment. Latent growth curve analysis (LCGA) was incorporated to determine trajectories of changes in PTSD across these assessments and whether several key clinical concerns for this population were associated with their treatment responses. Study Findings LCGA indicated three distinct trajectories in PTSD outcomes and identified several clinical factors that were prospectively linked with changes in veterans\u27 posttraumatic symptomatology. When compared to a group with high PTSD symptom severity that decreased over the program but relapsed at follow-up (41%), the near half (48.8%) of the sample with an improving trajectory had less combat exposure and superior physical/mental health. However, when compared to a minority (10.2%) with relatively low symptomatology that also remained somewhat stable, patients in the improving group were younger and also reported greater combat exposure, poorer physical/mental health status, and more problems with substance abuse before the start of treatment. Conclusions Findings suggest that veterans are most likely to benefit from residential treatment in an intermediate range of symptoms and risk factors, including PTSD symptom severity, history of combat exposure, and comorbid issues with physical/mental health. Addressing these factors in an integrative manner could help to optimize the effectiveness of treatments of combat-related PTSD in many cases

11CO2 Fixation: A Renaissance in PET Radiochemistry

Carbon-11 labelled carbon dioxide is the cyclotron-generated feedstock reagent for most positron emission tomography (PET) tracers using this radionuclide. Most carbon-11 labels, however, are installed using derivative reagents generated from [11C]CO2. In recent years, [11C]CO2 has seen a revival in applications for the direct incorporation of carbon-11 into functional groups such as ureas, carbamates, oxazolidinones, carboxylic acids, esters, and amides. This review summarizes classical [11C]CO2 fixation strategies using organometallic reagents and then focuses on newly developed methods that employ strong organic bases to reversibly capture [11C]CO2 into solution, thereby enabling highly functionalized labelled compounds to be prepared. Labelled compounds and radiopharmaceuticals that have been translated to the clinic are highlighted.Chemistry and Chemical Biolog

Sequence and expression analysis of rainbow trout CXCR2, CXCR3a and CXCR3b aids interpretation of lineage-specific conversion, loss and expansion of these receptors during vertebrate evolution

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved. Open Access funded by Biotechnology and Biological Sciences Research Council This work received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. Q.X. and Y.J. were supported financially by the National Scholarship Council of China, J.W.H by the Biotechnology and Biological Sciences Research Council (BB/K009125/1), and M.M.M. by European Commision LIFECYCLE project (222919).Peer reviewedPublisher PD

Chelate-free metal ion binding and heat-induced radiolabeling of iron oxide nanoparticles† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc02778g Click here for additional data file.

A novel reaction for chelate-free, heat-induced metal ion binding and radiolabeling of ultra-small paramagnetic iron oxide nanoparticles (USPIOs) has been established. Radiochemical and non-radioactive labeling studies demonstrated that the reaction has a wide chemical scope and is applicable to p-, d- and f-block metal ions with varying ionic sizes and formal oxidation states from 2+ to 4+. Radiolabeling studies found that 89Zr–Feraheme (89Zr–FH or 89Zr–ferumoxytol) can be isolated in 93 ± 3% radiochemical yield (RCY) and >98% radiochemical purity using size-exclusion chromatography. 89Zr–FH was found to be thermodynamically and kinetically stable in vitro using a series of ligand challenge and plasma stability tests, and in vivo using PET/CT imaging and biodistribution studies in mice. Remarkably, ICP-MS and radiochemistry experiments showed that the same reaction conditions used to produce 89Zr–FH can be employed with different radionuclides to yield 64Cu–FH (66 ± 6% RCY) and 111In–FH (91 ± 2% RCY). Electron magnetic resonance studies support a mechanism of binding involving metal ion association with the surface of the magnetite crystal core. Collectively, these data suggest that chelate-free labeling methods can be employed to facilitate clinical translation of a new class of multimodality PET/MRI radiotracers derived from metal-based nanoparticles. Further, this discovery is likely to have broader implications in drug delivery, metal separation science, ecotoxicology of nanoparticles and beyond

Reduction in Cerebral Blood Flow in Areas Appearing as White Matter Hyperintensities on Magnetic Resonance Imaging

The purpose of this study was to examine cerebral blood flow (CBF) as measured by arterial spin labeling (ASL) in tissue classified as white matter hyperintensities (WMH), normal appearing white matter, and grey matter. Seventeen healthy older adults received structural and ASL MRI. Cerebral blood flow was derived for three tissue types: WMH, normal appearing white matter, and grey matter. Cerebral blood flow was lower in WMH areas relative to normal appearing white matter, which in turn, was lower than grey matter. Regions with consistently lower CBF across individuals were more likely to appear as WMH. Results are consistent with an emerging literature linking diminished regional perfusion with the risk of developing WMH

Reduction in Cerebral Blood Flow in Areas Appearing as White Matter Hyperintensities on Magnetic Resonance Imaging

The purpose of this study was to examine cerebral blood flow (CBF) as measured by arterial spin labeling (ASL) in tissue classified as white matter hyperintensities (WMH), normal appearing white matter, and grey matter. Seventeen healthy older adults received structural and ASL MRI. Cerebral blood flow was derived for three tissue types: WMH, normal appearing white matter, and grey matter. Cerebral blood flow was lower in WMH areas relative to normal appearing white matter, which in turn, was lower than grey matter. Regions with consistently lower CBF across individuals were more likely to appear as WMH. Results are consistent with an emerging literature linking diminished regional perfusion with the risk of developing WMH

Reduction of CO\u3csub\u3e2\u3c/sub\u3e By a Masked Two-Coordinate Cobalt(I) Complex and Characterization of a Proposed Oxodicobalt(II) Intermediate

Fixation and chemical reduction of CO2 are important for utilization of this abundant resource, and understanding the detailed mechanism of C-O cleavage is needed for rational development of CO2 reduction methods. Here, we describe a detailed analysis of the mechanism of the reaction of a masked two-coordinate cobalt(i) complex, LtBuCo (where LtBu = 2,2,6,6-tetramethyl-3,5-bis[(2,6-diisopropylphenyl)imino]hept-4-yl), with CO2, which yields two products of C-O cleavage, the cobalt(i) monocarbonyl complex LtBuCo(CO) and the dicobalt(ii) carbonate complex (LtBuCo)2(μ-CO3). Kinetic studies and computations show that the κN,η6-arene isomer of LtBuCo rearranges to the κ2N,N′ binding mode prior to binding of CO2, which contrasts with the mechanism of binding of other substrates to LtBuCo. Density functional theory (DFT) studies show that the only low-energy pathways for cleavage of CO2 proceed through bimetallic mechanisms, and DFT and highly correlated domain-based local pair natural orbital coupled cluster (DLPNO-CCSD(T)) calculations reveal the cooperative effects of the two metal centers during facile C-O bond rupture. A plausible intermediate in the reaction of CO2 with LtBuCo is the oxodicobalt(II) complex LtBuCoOCoLtBu, which has been independently synthesized through the reaction of LtBuCo with N2O. The rapid reaction of LtBuCoOCoLtBu with CO2 to form the carbonate product indicates that the oxo species is kinetically competent to be an intermediate during CO2 cleavage by LtBuCo. LtBuCoOCoLtBu is a novel example of a thoroughly characterized molecular cobalt-oxo complex where the cobalt ions are clearly in the +2 oxidation state. Its nucleophilic reactivity is a consequence of high charge localization on the μ-oxo ligand between two antiferromagnetically coupled high-spin cobalt(ii) centers, as characterized by DFT and multireference complete active space self-consistent field (CASSCF) calculations

Cosmological Results from High-z Supernovae

The High-z Supernova Search Team has discovered and observed 8 new supernovae in the redshift interval z=0.3-1.2. These independent observations, confirm the result of Riess et al. (1998a) and Perlmutter et al. (1999) that supernova luminosity distances imply an accelerating universe. More importantly, they extend the redshift range of consistently observed SN Ia to z~1, where the signature of cosmological effects has the opposite sign of some plausible systematic effects. Consequently, these measurements not only provide another quantitative confirmation of the importance of dark energy, but also constitute a powerful qualitative test for the cosmological origin of cosmic acceleration. We find a rate for SN Ia of 1.4+/-0.5E-04 h^3/Mpc^3/yr at a mean redshift of 0.5. We present distances and host extinctions for 230 SN Ia. These place the following constraints on cosmological quantities: if the equation of state parameter of the dark energy is w=-1, then H0 t0 = 0.96+/-0.04, and O_l - 1.4 O_m = 0.35+/-0.14. Including the constraint of a flat Universe, we find O_m = 0.28+/-0.05, independent of any large-scale structure measurements. Adopting a prior based on the 2dF redshift survey constraint on O_m and assuming a flat universe, we find that the equation of state parameter of the dark energy lies in the range -1.48-1, we obtain w<-0.73 at 95% confidence. These constraints are similar in precision and in value to recent results reported using the WMAP satellite, also in combination with the 2dF redshift survey.Comment: 50 pages, AAS LateX, 15 figures, 15 tables. Accepted for publication by Astrophysical Journa

Rapid UBVRI Follow-up of the Highly Collimated Optical Afterglow of GRB010222

(Abridged) We present the earliest optical observations of the optical counterpart to the GRB 010222, obtained with the FLWO 1.2-m telescope in UBVRI passbands, starting 3.64 hours after the burst. We also present late R-band observations of the afterglow obtained with the 1.8-m VATT ~25 days after the burst. The temporal analysis of our data joined with published data indicates a steepening decay, independent of wavelength, asymptotically approaching t^{-0.80+/-0.05} at early times (t << 1 day) and t^{-1.30+/-0.05} at late times, with a sharp break at t_b=0.72+/-0.1 days. This is the second earliest observed break of any afterglow (after GRB 980519), which clearly indicates the importance of rapid multi-band follow-up for GRB afterglow research. The optical spectral energy distribution, corrected for small Galactic reddening, can be fit fairly well by a single power-law with a slope of -1.07+/-0.09. However, when we fit using our BVRI data only, we obtain a shallower slope of -0.88+/- 0.1, in excellent agreement with the slope derived from our low-resolution spectrum (-0.89 +/- 0.03). The spectral slope and light curve decay slopes we derive are not consistent with a jet model despite the presence of a temporal break. Significant host dust extinction with a star-burst reddening law would flatten the spectral index to match jet predictions and still be consistent with the observed spectral energy distribution. We derive an opening angle of 2.1 deg, smaller than any listed in the recent compilation of Frail et al. The total beamed energy corrected for the jet geometry is 4x10^50 erg, very close to the ``standard'' value of 5x10^50 erg found by Frail et al. for a number of other bursts with light-curve breaks.Comment: revised version (minor changes only) to be published in the ApJ Part 1, 12 pages, 4 figures; all data used for the fits and our CCD frames available at ftp://cfa-ftp.harvard.edu/pub/kstanek/GRB010222/ and through WWW at http://cfa-www.harvard.edu/cfa/oir/Research/GRB