Comparing Fixed-amount and Progressive-amount DRO Schedules for Tic Suppression in Youth with Chronic Tic Disorders

Chronic tic disorders (CTDs) involve motor and/or vocal tics that often cause substantial distress and impairment. Differential reinforcement of other behavior (DRO) schedules of reinforcement produce robust, but incomplete, reductions in tic frequency in youth with CTDs; however, a more robust reduction may be needed to affect durable clinical change. Standard, fixed‐amount DRO schedules have not commonly yielded such reductions, so we evaluated a novel, progressive‐amount DRO schedule, based on its ability to facilitate sustained abstinence from functionally similar behaviors. Five youth with CTDs were exposed to periods of baseline, fixed‐amount DRO (DRO‐F), and progressive‐amount DRO (DRO‐P). Both DRO schedules produced decreases in tic rate and increases in intertic interval duration, but no systematic differences were seen between the two schedules on any dimension of tic occurrence. The DRO‐F schedule was generally preferred to the DRO‐P schedule. Possible procedural improvements and other future directions are discussed

Depression, Relationship Quality, and Couples’ Demand/Withdraw and Demand/Submit Sequential Interactions

This study investigated the associations among depression, relationship quality, and demand/withdraw and demand/submit behavior in couples’ conflict interactions. Two 10-min conflict interactions were coded for each couple (N = 97) using Structural Analysis of Social Behavior (SASB; Benjamin, 1979a, 1987, 2000a). Depression was assessed categorically (via the presence of depressive disorders) and dimensionally (via symptom reports). Results revealed that relationship quality was negatively associated with demanding behavior, as well as receiving submissive or withdrawing behavior from one’s partner. Relationship quality was positively associated with withdrawal. Demanding behavior was positively associated with women’s depression symptoms but negatively associated with men’s depression symptoms. Sequential analysis revealed couples’ behavior was highly stable across time. Initiation of demand/withdraw and demand/submit sequences were negatively associated with partners’ relationship adjustment. Female demand/male withdraw was positively associated with men’s depression diagnosis. Results underscore the importance of sequential analysis when investigating associations among depression, relationship quality, and couples’ interpersonal behavior

Efficient calculation of carrier scattering rates from first principles

The electronic transport behaviour of materials determines their suitability for technological applications. We develop an efficient method for calculating carrier scattering rates of solid-state semiconductors and insulators from first principles inputs. The present method extends existing polar and non-polar electron-phonon coupling, ionized impurity, and piezoelectric scattering mechanisms formulated for isotropic band structures to support highly anisotropic materials. We test the formalism by calculating the electronic transport properties of 16 semiconductors and comparing the results against experimental measurements. The present work is amenable for use in high-throughput computational workflows and enables accurate screening of carrier mobilities, lifetimes, and thermoelectric power.Comment: 11 pages, 4 figures (SI: 21 pages, 14 figures

The Melanocortin-4 Receptor Integrates Circadian Light Cues and Metabolism

The melanocortin system directs diverse physiological functions from coat color to body weight homoeostasis. A commonality among melanocortin-mediated processes is that many animals modulate similar processes on a circannual basis in response to longer, summer days, suggesting an underlying link between circadian biology and the melanocortin system. Despite key neuroanatomical substrates shared by both circadian and melanocortin-signaling pathways, little is known about the relationship between the two. Here we identify a link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (Mc4r). Mc4r-deficient mice exhibit exaggerated circadian fluctuations in baseline blood glucose and glucose tolerance. Interestingly, exposure to lighting conditions that disrupt circadian rhythms improve their glucose tolerance. This improvement occurs through an increase in glucose clearance by skeletal muscle and is food intake and body weight independent. Restoring Mc4r expression to the paraventricular nucleus prevents the improvement in glucose tolerance, supporting a role for the paraventricular nucleus in the integration of circadian light cues and metabolism. Altogether these data suggest that Mc4r signaling plays a protective role in minimizing glucose fluctuations due to circadian rhythms and environmental light cues and demonstrate a previously undiscovered connection between circadian biology and glucose metabolism mediated through the melanocortin system

Probiotics: current landscape and future horizons

In recent years there has been a rapid rise in interest for the application of probiotic supplements to act as mediators in health and disease. This appeal is predominantly due to ever-increasing evidence of the interaction of the microbiota and pathophysiological processes of disease within the human host. This narrative review considers the current landscape of the probiotic industry and its research, and discusses current pitfalls in the lack of translation from laboratory science to clinical application. Future considerations into how industry and academia must adapt probiotic research to maximize success are suggested, including more targeted application of probiotic strains dependent on individual capabilities as well as application of multiple advanced analytical technologies to further understand and accelerate microbiome science. Lay abstract: The global market for probiotic supplements is continually expanding. Despite the public perception of benefits provided by probiotics, the evidence to conclusively link probiotic strains to improved characteristics of health or disease is lacking. This is owing, in part, to the lack of large-scale research trials, but also to the insufficient understanding of the interactions occurring within the human system following supplementation. More in-depth research into individual probiotic strains, combined with the application of multiple advanced measurement techniques will provide a future direction for probiotic research and, in turn, aim to provide useful data to translate into routine healthcare practice

Does Glass Size and Shape Influence Judgements of the Volume of Wine?

This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.0144536Background \ud Judgements of volume may influence the rate of consumption of alcohol and, in turn, the amount consumed. The aim of the current study was to examine the impact of the size and shape of wine glasses on perceptions of wine volume. \ud \ud Methods \ud Online experiment: Participants (n = 360; recruited via Mechanical Turk) were asked to match the volume of wine in two wine glasses, specifically: 1. the Reference glass holding a fixed reference volume, and 2. the Comparison glass, for which the volume could be altered until participants perceived it matched the reference volume. One of three comparison glasses was shown in each trial: ?wider? (20% wider but same capacity); ?larger? (same width but 25% greater capacity); or ?wider-and-larger? (20% wider and 25% greater capacity). Reference volumes were 125ml, 175ml and 250ml, in a fully factorial within-subjects design: 3 (comparison glass) x 3 (reference volume). Non-zero differences between the volumes with which participants filled comparison glasses and the corresponding reference volumes were identified using sign-rank tests. \ud \ud Results \ud Participants under-filled the wider glass relative to the reference glass for larger reference volumes, and over-filled the larger glass relative to the reference glass for all reference volumes. Results for the wider-and-larger glass showed a mixed pattern across reference volume. For all comparison glasses, in trials with larger reference volumes participants tended to fill the comparison glass less, relative to trials with smaller reference volumes for the same comparison glass.\ud \ud Conclusions \ud These results are broadly consistent with people using the relative fullness of glasses to judge volume, and suggest both the shape and capacity of wine glasses may influence perceived volume. Perceptions that smaller glasses contain more than larger ones (despite containing the same volume), could slow drinking speed and overall consumption by serving standard portions in smaller glasses. This hypothesis awaits testing.The study was funded by the Department of Health Policy Research Programme (http://prp.dh.gov.uk/) (Policy Research Unit in Behaviour and Health [PR-UN-0409-10109]). ASA and MRM are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research: Centre of Excellence. Funding from British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, and the National Institute for Health Research, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. None of the funders had a role in the study design, data collection, analysis, interpretation, or decision to submit for publication. The research was conducted independently of the funders, and the views expressed in this paper are those of the authors and not necessarily those of the funders

Identification of Burkholderia mallei and Burkholderia pseudomallei adhesins for human respiratory epithelial cells

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia pseudomallei </it>and <it>Burkholderia mallei </it>cause the diseases melioidosis and glanders, respectively. A well-studied aspect of pathogenesis by these closely-related bacteria is their ability to invade and multiply within eukaryotic cells. In contrast, the means by which <it>B. pseudomallei </it>and <it>B. mallei </it>adhere to cells are poorly defined. The purpose of this study was to identify adherence factors expressed by these organisms.</p> <p>Results</p> <p>Comparative sequence analyses identified a gene product in the published genome of <it>B. mallei </it>strain ATCC23344 (locus # BMAA0649) that resembles the well-characterized <it>Yersinia enterocolitica </it>autotransporter adhesin YadA. The gene encoding this <it>B. mallei </it>protein, designated <it>boaA</it>, was expressed in <it>Escherichia coli </it>and shown to significantly increase adherence to human epithelial cell lines, specifically HEp2 (laryngeal cells) and A549 (type II pneumocytes), as well as to cultures of normal human bronchial epithelium (NHBE). Consistent with these findings, disruption of the <it>boaA </it>gene in <it>B. mallei </it>ATCC23344 reduced adherence to all three cell types by ~50%. The genomes of the <it>B. pseudomallei </it>strains K96243 and DD503 were also found to contain <it>boaA </it>and inactivation of the gene in DD503 considerably decreased binding to monolayers of HEp2 and A549 cells and to NHBE cultures.</p> <p>A second YadA-like gene product highly similar to BoaA (65% identity) was identified in the published genomic sequence of <it>B. pseudomallei </it>strain K96243 (locus # BPSL1705). The gene specifying this protein, termed <it>boaB</it>, appears to be <it>B. pseudomallei</it>-specific. Quantitative attachment assays demonstrated that recombinant <it>E. coli </it>expressing BoaB displayed greater binding to A549 pneumocytes, HEp2 cells and NHBE cultures. Moreover, a <it>boaB </it>mutant of <it>B. pseudomallei </it>DD503 showed decreased adherence to these respiratory cells. Additionally, a <it>B. pseudomallei </it>strain lacking expression of both <it>boaA </it>and <it>boaB </it>was impaired in its ability to thrive inside J774A.1 murine macrophages, suggesting a possible role for these proteins in survival within professional phagocytic cells.</p> <p>Conclusions</p> <p>The <it>boaA </it>and <it>boaB </it>genes specify adhesins that mediate adherence to epithelial cells of the human respiratory tract. The <it>boaA </it>gene product is shared by <it>B. pseudomallei </it>and <it>B. mallei </it>whereas BoaB appears to be a <it>B. pseudomallei</it>-specific adherence factor.</p

Designing transparent conductors using forbidden optical transitions

Many semiconductors present weak or forbidden transitions at their fundamental band gaps, inducing a widened region of transparency. This occurs in high-performing n-type transparent conductors (TCs) such as Sn-doped In2O3 (ITO), however thus far the presence of forbidden transitions has been neglected in searches for new p-type TCs. To address this, we first compute high-throughput absorption spectra across ~18,000 semiconductors, showing that over half exhibit forbidden or weak optical transitions at their band edges. Next, we demonstrate that compounds with highly localized band edge states are more likely to present forbidden transitions. Lastly, we search this set for p-type and n-type TCs with forbidden or weak transitions. Defect calculations yield unexplored TC candidates such as ambipolar BeSiP2, Zr2SN2 and KSe, p-type BAs, Au2S, and AuCl, and n-type Ba2InGaO5, GaSbO4, and KSbO3, among others. We share our data set via the MPContribs platform, and we recommend that future screenings for optical properties use metrics representative of absorption features rather than band gap alone

Structural modification of the Pseudomonas aeruginosa alkylquinoline cell–cell communication signal, HHQ, leads to benzofuranoquinolines with anti-virulence behaviour in ESKAPE pathogens

Microbial populations have evolved intricate networks of negotiation and communication through which they can coexist in natural and host ecosystems. The nature of these systems can be complex and they are, for the most part, poorly understood at the polymicrobial level. The Pseudomonas Quinolone Signal (PQS) and its precursor 4- hydroxy- 2-heptylquinoline (HHQ) are signal molecules produced by the important nosocomial pathogen Pseudomonas aeruginosa. They are known to modulate the behaviour of co-colonizing bacterial and fungal pathogens such as Bacillus atropheaus, Candida albicans and Aspergillus fumigatus. While the structural basis for alkyl-quinolone signalling within P. aeruginosa has been studied extensively, less is known about how structural derivatives of these molecules can influ-ence multicellular behaviour and population- level decision-making in other co-colonizing organisms. In this study, we investigated a suite of small molecules derived initially from the HHQ framework, for anti-virulence activity against ESKAPE pathogens, at the species and strain levels. Somewhat surprisingly, with appropriate substitution, loss of the alkyl chain (present in HHQ and PQS) did not result in a loss of activity, presenting a more easily accessible synthetic framework for investigation. Virulence profiling uncovered significant levels of inter-strain variation among the responses of clinical and environmental isolates to small-molecule challenge. While several lead compounds were identified in this study, further work is needed to appreciate the extent of strain- level tolerance to small-molecule anti-infectives among pathogenic organisms.National Forum for the Enhancement of Teaching and Learning in Higher Education SFI/12/IP/1315, US Cystic Fibrosis Foundation SFI/12/RC/2275, National Health and Medical Research Council (NHMRC) of Australia SFI/12/RC/2275_P2, UCC Strategic Research Fund and Science Foundation Ireland (SFI) SSPC-3 12/RC/2275_2, Synthesis and Solid State Pharmaceutical Centre (SSPC) HRB-ILP-POR-2019-004, MRCG-2018-16, Universidade do Algarve TL19UCC1481/02, OGARA1710, APP1183640 2020-5,info:eu-repo/semantics/publishedVersio

Introduction to "Working Across Species"

Comparison between different animal species is omnipresent in the history of science and medicine but rarely subject to focussed historical analysis. The articles in the ‘‘Working Across Species’’ topical collection address this deficit by looking directly at the practical and epistemic work of cross-species comparison. Drawn from papers presented at a Wellcome-Trust-funded workshop in 2016, these papers investigate various ways that comparison has been made persuasive and successful, in multiple locations, by diverse disciplines, over the course of two centuries. They explore the many different animal features that have been considered to be (or else made) comparable, and the ways that animals have shaped science and medicine through the use of comparison. Authors demonstrate that comparison between species often transcended the range of practices typically employed with experimental animal models, where standardised practises and apparatus were applied to standardised bodies to produce generalizable, objective data; instead, comparison across species has often engaged diverse groups of nonstandard species, made use of subjective inferences about phenomena that cannot be directly observed, and inspired analogies that linked physiological and behavioural characteristics with the apparent affective state of non-human animals. Moreover, such comparative practices have also provided unusually fruitful opportunities for collaborative connections between different research traditions and disciplines