260 research outputs found
Effects of stimulants and atomoxetine on emotional lability in adults:a systematic review and meta-analysis
Background: Emotional lability (EL) is an associated feature of attention-deficit/hyperactivity disorder (ADHD) in adults, contributing to functional impairment. Yet the effect of pharmacological treatments for ADHD on EL symptoms is unknown. We conducted a systematic review and meta-analysis to examine the effects of stimulants and atomoxetine on symptoms of EL and compare these with the effects on core ADHD symptoms. Methods: A systematic search was conducted on the databases Embase, PsychInfo, and Ovid Medline® and the clinicaltrials.gov website. We included randomised, double-blind, placebo-controlled trials of stimulants and atomoxetine in adults aged 18–60 years, with any mental health diagnosis characterised by emotional or mood instability, with at least one outcome measure of EL. All identified trials were on adults with ADHD. A random-effects meta-analysis with standardised mean difference and 95% confidence intervals was used to investigate the effect size on EL and compare this to the effect on core ADHD symptoms. Results: Of the 3,864 publications identified, nine trials met the inclusion criteria for the meta-analysis. Stimulants and atomoxetine led to large mean weighted effect-sizes for on ADHD symptoms (n = 9, SMD = −0.8, 95% CI:−1.07 to −0.53). EL outcomes showed more moderate but definite effects (n = 9, SMD = −0.41, 95% CI:−0.57 to −0.25). Conclusions: In this meta-analysis, stimulants and atomoxetine were moderately effective for EL symptoms, while effect size on core ADHD symptoms was twice as large. Methodological issues may partially explain the difference in effect size. Reduced average effect size could also reflect heterogeneity of EL with ADHD pharmacotherapy responsive and non-responsive sub-types. Our findings indicate that EL may be less responsive than ADHD symptoms overall, perhaps indicating the need for adjunctive psychotherapy in some cases. To clarify these questions, our findings need replication in studies selecting subjects for high EL and targeting EL as the primary outcome
Louse (Insecta : Phthiraptera) mitochondrial 12S rRNA secondary structure is highly variable
Lice are ectoparasitic insects hosted by birds and mammals. Mitochondrial 12S rRNA sequences obtained from lice show considerable length variation and are very difficult to align. We show that the louse 12S rRNA domain III secondary structure displays considerable variation compared to other insects, in both the shape and number of stems and loops. Phylogenetic trees constructed from tree edit distances between louse 12S rRNA structures do not closely resemble trees constructed from sequence data, suggesting that at least some of this structural variation has arisen independently in different louse lineages. Taken together with previous work on mitochondrial gene order and elevated rates of substitution in louse mitochondrial sequences, the structural variation in louse 12S rRNA confirms the highly distinctive nature of molecular evolution in these insects
Statistical Theory of Spin Relaxation and Diffusion in Solids
A comprehensive theoretical description is given for the spin relaxation and
diffusion in solids. The formulation is made in a general
statistical-mechanical way. The method of the nonequilibrium statistical
operator (NSO) developed by D. N. Zubarev is employed to analyze a relaxation
dynamics of a spin subsystem. Perturbation of this subsystem in solids may
produce a nonequilibrium state which is then relaxed to an equilibrium state
due to the interaction between the particles or with a thermal bath (lattice).
The generalized kinetic equations were derived previously for a system weakly
coupled to a thermal bath to elucidate the nature of transport and relaxation
processes. In this paper, these results are used to describe the relaxation and
diffusion of nuclear spins in solids. The aim is to formulate a successive and
coherent microscopic description of the nuclear magnetic relaxation and
diffusion in solids. The nuclear spin-lattice relaxation is considered and the
Gorter relation is derived. As an example, a theory of spin diffusion of the
nuclear magnetic moment in dilute alloys (like Cu-Mn) is developed. It is shown
that due to the dipolar interaction between host nuclear spins and impurity
spins, a nonuniform distribution in the host nuclear spin system will occur and
consequently the macroscopic relaxation time will be strongly determined by the
spin diffusion. The explicit expressions for the relaxation time in certain
physically relevant cases are given.Comment: 41 pages, 119 Refs. Corrected typos, added reference
The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): A randomised placebo-controlled trial
Background: Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted. Methods: Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at six months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at six months adjusted for baseline score, allocation group and site. Results: The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at six months, of whom 21 (72%) were included in the mITT analysis. At six months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at six months was -3.86 (95% Confidence Intervals = -10.04 to 2.32, p=0.22). There were 14 serious adverse events; six in the clozapine arm and eight in the placebo arm of the trial. There was little difference in the cost of care between groups. Interpretation: We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units. Trial registration ISRCTN18352058. https://doi.org/10.1186/ISRCTN1835205
X-ray Survey Results on Active Galaxy Physics and Evolution
This "pedagogical" review describes the key Chandra and XMM-Newton
extragalactic surveys to date and details some of their implications for AGN
physics and evolution. We additionally highlight two topics of current
widespread interest: (1) X-ray constraints on the AGN content of luminous
submillimeter galaxies, and (2) the demography and physics of high-redshift (z
> 4) AGN as revealed by X-ray observations. Finally, we discuss prospects for
future X-ray surveys with Chandra, XMM-Newton, and upcoming missions.Comment: 26 pages, in Physics of Active Galactic Nuclei at All Scales, eds.
Alloin D., Johnson R., Lira P. (Springer-Verlag, Berlin), version with all
figures at http://www.astro.psu.edu/users/niel/papers/papers.htm
Effects of rapid antigen degradation and VEE glycoprotein specificity on immune responses induced by a VEE replicon vaccine
Genetic vaccines are engineered to produce immunogens de novo in the cells of the host for stimulation of a protective immune response. In some of these systems, antigens engineered for rapid degradation have produced an enhanced cellular immune response by more efficient entry into pathways for processing and presentation of MHC class I peptides. VEE replicon particles (VRP), single cycle vaccine vectors derived from Venezuelan equine encephalitis virus (VEE), are examined here for the effect of an increased rate of immunogen degradation on VRP vaccine efficacy. VRP expressing the matrix capsid (MA/CA) portion of SIV Gag were altered to promote rapid degradation of MA/CA by various linkages to co-translated ubiquitin or by destabilizing mutations and were used to immunize BALB/c mice for quantitation of the anti-MA/CA cellular and humoral immune responses. Rapid degradation by the N-end rule correlated with a dampened immune response relative to unmodified MA/CA when the VRP carried a glycoprotein spike from an attenuated strain of VEE. In contrast, statistically equivalent numbers of IFNγ+ T-cells resulted when VRP expressing unstable MA/CA were packaged with the wild-type VEE glycoproteins. These results suggest that the cell types targeted in vivo by VRP carrying mutant or wild type glycoprotein spikes are functionally different, and are consistent with previous findings suggesting that wild-type VEE glycoproteins preferentially target professional antigen presenting cells that use peptides generated from the degraded antigen for direct presentation on MHC
- …