The effect of hair color on the incorporation of codeine into human hair.

The influence of melanin on the binding of xenobiotics in hair will impact the interpretation of drug concentrations determined by hair testing. The purpose of this study was to determine if codeine, as a model compound of abused drugs, would be incorporated into black, brown, blond, or red hair as a function of melanin concentration. Such data would assist in the interpretation of codeine concentrations in hair and help elucidate the potential influence of hair color on incorporation of drugs. Male and female Caucasians with black (n = 6), brown (n = 12), blond (n = 8), or red hair (n = 6) and non-Caucasians with black hair (n = 12) aged 21-40 years were enrolled in the study. Each subject was administered oral codeine phosphate syrup in a dosage of 30 mg three times a day for five days. Twenty-four hours after the end of the treatment period, a 30-mg codeine dose was administered and the subject's plasma area under the concentration time curve (AUC) for codeine was determined. Codeine and melanin were measured in the first 3 cm of hair closest to the vertex region of the scalp prior to and 1, 4, 5, 6, and 7 weeks after dosing. The quantitative and qualitative melanin profiles were determined for each subject's hair to provide an objective measure of hair color. The plasma concentrations of codeine were measured to eliminate differences in the bioavailability and clearance of codeine as factors that might account for the differences in codeine hair concentrations. The subjects were asked not to cut their hair in the vertex region of the scalp or to use any form of chemical treatment on their hair, but otherwise normal hygienic measures were permitted. The mean (+/- SE) hair codeine concentrations 5 weeks after dosing were 1429 (+/- 249) pg/mg in black hair; 208 (+/- 17) pg/mg in brown hair; 99 (+/- 10) pg/mg in blond hair; and 69 (+/- 11) in red hair pg/mg. In black hair, codeine concentrations were 2564 (+/- 170) pg/mg for Asians and 865 (+/- 162) pg/mg for Caucasians. Similar concentration relationships were observed at weeks 4, 6, and 7. A strong relationship between the hair concentrations of codeine and melanin (R(2) = 0.73) was observed. Normalization of the codeine concentration with the melanin concentration reduced the hair color differences observed. These data demonstrate that the interpretation and reporting of hair test results for codeine are influenced by hair color. After this dosing protocol, the proposed federal guideline cutoff of 200 pg/mg of codeine would result in 100% of subjects with black hair and 50% of subjects with brown hair being reported as positive, and subjects with blond or red hair would be reported as negative. The incorporation of these drugs into hair should be studied carefully in humans to ensure the appropriate interpretation of drug concentrations

Rivastigmine decreases brain damage in HIV patients with mild cognitive deficits.

Rivastigmine has been shown to improve cognition in HIV+ patients with minor neurocognitive disorders; however, the mechanisms underlying such beneficial effect are currently unknown. To assess whether rivastigmine therapy is associated with decreased brain inflammation and damage, we performed T1/T2* relaxometry and magnetization transfer imaging in 17 aviremic HIV+ patients with minor neurocognitive disorders enrolled on a crossed over randomized rivastigmine trial. Rivastigmine therapy was associated with changes in MRI metrics indicating a decrease in brain water content (i.e., edema reabsorption) and/or reduced demyelination/axonal damage. Furthermore, MRI changes correlated with cognitive improvement on rivastigmine therapy

Coupling Optical and Electrical Measurements in Artificial Membranes: Lateral Diffusion of Lipids and Channel Forming Peptides in Planar Bilayers

Planar lipid bilayers (PLB) were prepared by the Montal-Mueller technique in a FRAP system designed to simultaneously measure conductivity across, and lateral diffusion of, the bilayer. In the first stage of the project the FRAP system was used to characterise the lateral dynamics of bilayer lipids with regards to phospholipid composition (headgroup, chain unsaturation etc.), presence of cholesterol and the effect of divalent cations on negatively-charged bilayers. In the second stage of the project, lateral diffusion of two fluorescently-labelled voltage-dependent pore-forming peptides (alamethicin and S4s from Shaker K(+) channel) was determined at rest and in the conducting state. This study demonstrates the feasibility of such experiments with PLBs, amenable to physical constraints, and thus offers new opportunities for systematic studies of structure-function relationships in membrane-associating molecules

Azimuthal anisotropy of K0s and Lambda prduction at mid-rapidity from Au+Au collisions at root s = 130 GeV

We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, L and Lbar at midrapidity in Au+Au collisions at sNN = 130 GeV at RHIC. The value of v2 as a function of transverse momentum of the produced particles pt and collision centrality is presented for both particles up to pt 3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.Comment: 6 pages, 4 figures, by the STAR collaboratio

In search of disorders: internalizing symptom networks in a large clinical sample.

Background The co‐occurrence of internalizing disorders is a common form of psychiatric comorbidity, raising questions about the boundaries between these diagnostic categories. We employ network psychometrics in order to: (a) determine whether internalizing symptoms cluster in a manner reflecting DSM diagnostic criteria, (b) gauge how distinct these diagnostic clusters are and (c) examine whether this network structure changes from childhood to early and then late adolescence. Method Symptom‐level data were obtained for service users in publicly funded mental health services in England between 2011 and 2015 (N = 37,162). A symptom network (i.e. Gaussian graphical model) was estimated, and a community detection algorithm was used to explore the clustering of symptoms. Results The estimated network was densely connected and characterized by a multitude of weak associations between symptoms. Six communities of symptoms were identified; however, they were weakly demarcated. Two of these communities corresponded to social phobia and panic disorder, and four did not clearly correspond with DSM diagnostic categories. The network structure was largely consistent by sex and across three age groups (8–11, 12–14 and 15–18 years). Symptom connectivity in the two older age groups was significantly greater compared to the youngest group and there were differences in centrality across the age groups, highlighting the age‐specific relevance of certain symptoms. Conclusions These findings clearly demonstrate the interconnected nature of internalizing symptoms, challenging the view that such pathology takes the form of distinct disorders

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

K⋆(892)0K^{\star}(892)^{0} Production in Relativistic Heavy Ion Collisions at sNN=130\sqrt{s_{_{NN}}}=130 GeV

We report the first observation of $K^{\star}(892)^{0}\to\pi K$ in relativistic heavy ion collisions. The transverse momentum spectrum of $(K^{\star0}+\bar{K}^{\star0})/2$ from central Au+Au collisions at $\sqrt{s_{_{NN}}}=130$ GeV is presented. The ratios of the $K^{\star0}$ yield derived from these data to the yields of negative hadrons, charged kaons, and $\phi$ mesons have been measured in central and minimum bias collisions and compared with model predictions and comparable $e^{+}e^{-}$, $pp$, and $\bar{p}p$ results. The data indicate no dramatic reduction of $K^{\star0}$ production in relativistic heavy ion collisions despite expected losses due to rescattering effects.Comment: 6 pages, 3 figures, To be published in PRC

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society