Lynggaardavery3432

We report a new "switched-suppression" effect for conditionals with negated components, for example, "if she had not watered the plants they would not have bloomed" modus tollens is suppressed by alternatives and denial of the antecedent by additional conditions, rather than vice versa (Experiments 3a and 3b). We discuss the implications of the results for alternative theories of conditional reasoning. © 2020 Cognitive Science Society, Inc.OBJECTIVES Age-related hearing loss (ARHL) is a prevalent condition associated with increased risk for depression and cognitive decline. This 12-week prospective, double-blind pilot randomized controlled trial (RCT) of hearing aids (HAs) for depressed older adults with ARHL evaluated the feasibility of a novel research design. METHODS/DESIGN N = 13 individuals aged ≥60 years with Major Depressive Disorder or Persistent Depressive Disorder and at least mild hearing loss (pure tone average ≥ 30 dB) were randomized to receive full- (active) vs low-amplification (sham) HAs added to psychiatric treatment as usual. Duration of HA use in hours/day, adverse events frequency, attrition rate, and maintenance of the study blinding were the primary outcome measures. RESULTS Compliance with HAs was excellent (>9 hours/day for both groups) and rates of adverse events and drop-outs did not differ between groups. Preliminary data demonstrated differential improvement for active vs sham HAs on hearing functioning (Hearing Handicap Inventory for the Elderly [nonparametric effect size (np-ES) = 0.62]), depressive symptoms (Inventory for Depressive Symptomatology [np-ES = 0.31]), cognition (Repeatable Battery for the Assessment of Neuropsychological Status Immediate Memory [np-ES = 0.25]), and general functioning (World Health Organization Disability Assessment Schedule [np-ES = 0.53]). Significantly greater than 50% of both groups correctly guessed their treatment assignment, indicating incomplete concealment of treatment allocation. CONCLUSIONS This pilot RCT for ARHL and late-life depression was feasible to execute and showed clinical promise, but improved methods of blinding the experimental treatments are needed. Larger studies should investigate whether hearing remediation may be an effective preventative and/or therapeutic strategy for late-life depression and cognitive decline. © 2020 John Wiley & Sons Ltd.The structural poses of ligands that bind weakly to protein receptors are challenging to define. In this work we have studied ligand interactions with the adrenoreceptor (AR) subtypes, α 1A -AR and α 1B -AR which belong to the G-protein coupled receptor (GPCR) superfamily by employing the solution-based ligand-observed NMR method INPHARMA (Interligand Noes for PHARmacophore Mapping). Lack of receptor crystal structures and of subtype-selective drugs has hindered the definition of the physiological roles of each subtype and limited drug development. We determined the binding pose of the weak binding α 1A -AR selective agonist, A-61603, relative to an endogenous agonist, epinephrine, at both α 1A -AR and α 1B -AR. The NMR experimental data were quantitatively compared, using SpINPHARMA, to the back-calculated spectra based on ligand poses obtained from all-atom molecular dynamics simulations. The results helped mechanistically explain the selectivity of ( R )-A-61603 towards α 1A -AR, demonstrating an approach for targeting subtype selectivity in ARs. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Circadian clocks are cell autonomous self-sustaining oscillators that allow organisms to anticipate environmental changes throughout the solar day and persist in nearly every cell examined. Environmental or genetic disruption of circadian rhythms increases the risk of several types of cancer, but the underlying mechanisms are not well understood. Here, we discuss evidence connecting circadian rhythms - with emphasis on the cryptochrome proteins (CRY1/2) - to cancer through in vivo models, mechanisms involving known tumor suppressors and oncogenes, chemotherapeutic efficacy, and human cancer risk. This article is protected by copyright. All rights reserved.BACKGROUND AND AIM The association of fecal calprotectin (FC) and endoscopic response in inflammatory bowel disease patients during vedolizumab (VDZ) treatment is largely unknown. The aim of this study is to assess the diagnostic value of FC to predict endoscopic response. METHODS Patients with active endoscopic disease at baseline were included. Endoscopies and FC tests were performed at baseline and week 16. Patients with a confirmed endoscopic response at week 16, continued VDZ maintenance therapy and endoscopy and FC tests were performed at week 52. Endoscopic response was defined as endoscopic Mayo score reduction of ≥1, SES-CD of ≥50% or Rutgeerts of ≥1. Correlations were assessed using Spearman and receiver operating characteristic statistics. RESULTS A total of 114; 46 ulcerative colitis and 68 Crohn's disease patients (44 males, median age 40 years) were included after start of VDZ; 85% was anti-TNFα refractory. SCH-527123 in vivo Endoscopic response was observed in 60 (53%) patients at week 16, the response sustained in 73% at week 52. FC decreased significantly from 819 at baseline to 154 μg/g at week 16. FC at week 16 and 52 were significantly correlated to (sustained) endoscopic response (r-0.62/r-0.67,p400μg/g after induction indicates endoscopic loss of response. This simple FC algorithm may guide clinical decisions on the continuation and optimization of VDZ in IBD patients. This article is protected by copyright. All rights reserved.Student pastoral support is crucial throughout medical training and is often conducted via face to face meetings with academic personal tutors or mentors. However, the sudden introduction of social distancing measures designed to stem the spread of the virus resulted in a national switch to online teaching and removed the ability to provide students with support in-person. This rapid and unexpected change of circumstances and loss of structure left many students socially isolated and struggling to cope with massive uncertainty. This article is protected by copyright. All rights reserved.