Anxiety sensitivity as a predictor of outcome in the treatment of obsessive-compulsive disorder

BACKGROUND AND OBJECTIVES: To address the fact that not all individuals who receive cognitive-behavioral therapy (CBT) for obsessive-compulsive disorder (OCD) exhibit complete symptom reduction, research has examined factors that predict outcome; however, no studies have examined anxiety sensitivity (AS) as a predictor of outcome of CBT for OCD. AS refers to the fear of anxious arousal that results from mistaken beliefs about the dangerousness of anxiety-related body sensations. It is important to understand whether AS influences OCD treatment outcome, considering that (a) some obsessions directly relate to AS, and (b) OCD patients with high AS may be reluctant to engage in anxiety-provoking components of CBT for OCD. METHODS: Patients (N = 187) with a primary diagnosis of OCD who received residential CBT for OCD participated in this study, which involved completing a self-report battery at pre- and post-treatment. RESULTS: Results supported study hypotheses, in that (a) baseline AS positively correlated with baseline OCD severity, and (b) greater baseline AS prospectively predicted higher posttreatment OCD symptom severity even after controlling for pretreatment OCD and depression severity. LIMITATIONS: The study was limited by its use of an older measure of AS, reliance on self-report measures, and nonstandardized treatment across participants. CONCLUSIONS: Findings highlight the importance of AS in the nature and treatment of OCD. Clinical implications and future directions are discussed

Personality Characteristics and Experiential Avoidance in Trichotillomania: Results from an Age and Gender Matched Sample

Despite its prevalence and a growing body of research, significant gaps remain in the knowledge of trichotillomania (TTM). The current study sought to address this issue by examining personality characteristics, impulsivity, and experiential avoidance of those with TTM compared to an age and gender matched sample. 56 Female participants (28 with TTM and 28 non-clinical age-matched controls) completed the Personality Assessment Inventory (PAI), Barratt\u27s Impulsivity Scale (BIS), and the Acceptance and Action Questionnaire (AAQ). Paired-sample t-tests compared each of the 28 individuals who met criteria for TTM to an age and gender matched individual who did not meet criteria for TTM or any Axis I condition. Significant differences were found between many of the PAI scales and subscales, impulsivity, and experiential avoidance. The TTM group displayed higher levels of pathology than the control group. The findings provide evidence that individuals with TTM demonstrate differing levels of personality characteristics compared to individuals without TTM and that treatment may benefit from acknowledging and targeting these areas

Increasing the density of nanomedicines improves their ultrasound-mediated delivery to tumours

AbstractNanomedicines have provided fresh impetus in the fight against cancer due to their selectivity and power. However, these agents are limited when delivered intravenously due to their rapid clearance from the bloodstream and poor passage from the bloodstream into target tumours. Here we describe a novel stealthing strategy which addresses both these limitations and thereby demonstrate that both the passive and mechanically-mediated tumour accumulation of the model nanomedicine adenovirus (Ad) can be substantially enhanced. In our strategy gold nanoparticles were thoroughly modified with 2kDa polyethyleneglycol (PEG) and then linked to Ad via a single reduction-cleavable 5kDa PEG. The resulting Ad–gold–PEG construct was compared to non-modified Ad or conventionally stealthed Ad–poly[N-(2-hydroxypropyl)methacrylamide] (Ad–PHPMA). Notably, although Ad–gold–PEG was of similar size and surface charge to Ad–PHPMA the increase in density, resulting from the inclusion of the gold nanoparticles, provided a substantial enhancement of ultrasound-mediated transport. In an in vitro tumour mimicking phantom, the level and distance of Ad–gold–PEG transport was shown to be substantially greater than achieved with Ad–PHPMA. In in vivo studies 0.1% of an unmodified Ad dose was shown to accumulate in tumours, whereas over 12% of the injected dose was recovered from the tumours of mice treated with Ad–gold–PEG and ultrasound. Ultimately, a significant increase in anti-tumour efficacy resulted from this strategy. This stealthing and density-increasing technology could ultimately enhance clinical utility of intravenously delivered nanoscale medicines including viruses, liposomes and antibodies

Advancing Paternal Age Is Associated with Deficits in Social and Exploratory Behaviors in the Offspring: A Mouse Model

Background: Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring. Methods: C57BL/6J offspring (n = 12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n = 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring. Principal Findings: The offspring of older fathers were found to engage in significantly less social (p = 0.02) and exploratory (p = 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity. Conclusions: Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigeneti

An Empirical Model For Intrinsic Alignments: Insights From Cosmological Simulations

We extend current models of the halo occupation distribution (HOD) to include a flexible, empirical framework for the forward modeling of the intrinsic alignment (IA) of galaxies. A primary goal of this work is to produce mock galaxy catalogs for the purpose of validating existing models and methods for the mitigation of IA in weak lensing measurements. This technique can also be used to produce new, simulation-based predictions for IA and galaxy clustering. Our model is probabilistically formulated, and rests upon the assumption that the orientations of galaxies exhibit a correlation with their host dark matter (sub)halo orientation or with their position within the halo. We examine the necessary components and phenomenology of such a model by considering the alignments between (sub)halos in a cosmological dark matter only simulation. We then validate this model for a realistic galaxy population in a set of simulations in the Illustris-TNG suite. We create an HOD mock with Illustris-like correlations using our method, constraining the associated IA model parameters, with the $\chi^2_{\rm dof}$ between our model's correlations and those of Illustris matching as closely as 1.4 and 1.1 for orientation--position and orientation--orientation correlation functions, respectively. By modeling the misalignment between galaxies and their host halo, we show that the 3-dimensional two-point position and orientation correlation functions of simulated (sub)halos and galaxies can be accurately reproduced from quasi-linear scales down to $0.1~h^{-1}{\rm Mpc}$. We also find evidence for environmental influence on IA within a halo. Our publicly-available software provides a key component enabling efficient determination of Bayesian posteriors on IA model parameters using observational measurements of galaxy-orientation correlation functions in the highly nonlinear regime.Comment: 17 pages, 12 figures, 3 tables, for submission to The Open Journal of Astrophysics, code available at https://github.com/astropy/halotool

Wide-field Multi-object Spectroscopy to Enhance Dark Energy Science from LSST

LSST will open new vistas for cosmology in the next decade, but it cannot reach its full potential without data from other telescopes. Cosmological constraints can be greatly enhanced using wide-field ($>20$ deg$^2$ total survey area), highly-multiplexed optical and near-infrared multi-object spectroscopy (MOS) on 4-15m telescopes. This could come in the form of suitably-designed large surveys and/or community access to add new targets to existing projects. First, photometric redshifts can be calibrated with high precision using cross-correlations of photometric samples against spectroscopic samples at $0 < z < 3$ that span thousands of sq. deg. Cross-correlations of faint LSST objects and lensing maps with these spectroscopic samples can also improve weak lensing cosmology by constraining intrinsic alignment systematics, and will also provide new tests of modified gravity theories. Large samples of LSST strong lens systems and supernovae can be studied most efficiently by piggybacking on spectroscopic surveys covering as much of the LSST extragalactic footprint as possible (up to $\sim20,000$ square degrees). Finally, redshifts can be measured efficiently for a high fraction of the supernovae in the LSST Deep Drilling Fields (DDFs) by targeting their hosts with wide-field spectrographs. Targeting distant galaxies, supernovae, and strong lens systems over wide areas in extended surveys with (e.g.) DESI or MSE in the northern portion of the LSST footprint or 4MOST in the south could realize many of these gains; DESI, 4MOST, Subaru/PFS, or MSE would all be well-suited for DDF surveys. The most efficient solution would be a new wide-field, highly-multiplexed spectroscopic instrument in the southern hemisphere with $>6$m aperture. In two companion white papers we present gains from deep, small-area MOS and from single-target imaging and spectroscopy.Comment: Submitted to the call for Astro2020 science white papers; tables with estimates of telescope time needed for a supernova host survey can be seen at http://d-scholarship.pitt.edu/id/eprint/3604

Quality of private and public ambulatory health care in low and middle income countries: systematic review of comparative studies

Paul Garner and colleagues conducted a systematic review of 80 studies to compare the quality of private versus public ambulatory health care in low- and middle-income countries

The Evolutionary Fates of a Large Segmental Duplication in Mouse

Gene duplication and loss are major sources of genetic polymorphism in populations, and are important forces shaping the evolution of genome content and organization. We have reconstructed the origin and history of a 127-kbp segmental duplication, R2d, in the house mouse (Mus musculus). R2d contains a single protein-coding gene, Cwc22. De novo assembly of both the ancestral (R2d1) and the derived (R2d2) copies reveals that they have been subject to nonallelic gene conversion events spanning tens of kilobases. R2d2 is also a hotspot for structural variation: its diploid copy number ranges from zero in the mouse reference genome to >80 in wild mice sampled from around the globe. Hemizygosity for high copy-number alleles of R2d2 is associated in cis with meiotic drive; suppression of meiotic crossovers; and copy-number instability, with a mutation rate in excess of 1 per 100 transmissions in some laboratory populations. Our results provide a striking example of allelic diversity generated by duplication and demonstrate the value of de novo assembly in a phylogenetic context for understanding the mutational processes affecting duplicate genes