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IntroductionChildren with Attention Deficit/Hyperactivity Disorder (ADHD) participated in a randomized clinical trial comparing animal-assisted intervention (AAI) to psychosocial treatment as usual (TAU). This brief report describes effects of AAI on acute HPA axis reactivity and regulation. Saliva was collected before, during, and after psychosocial intervention sessions with and without therapy dogs and later assayed for cortisol (ug/dL).MethodologyThirty-nine participants (n = 39) with ADHD, aged 7-9 years (79% male) provided saliva at 3 points during 90-minute sessions; (i) upon arrival, (ii) +20 minutes, and (iii) 15 minutes prior to departure, on 3 occasions across an 8-week intervention (weeks 1, 4, and 8). Cortisol slopes calculated within each session were compared across the intervention weeks to determine within subject and between group effect sizes. Spearman’s correlations between baseline individual neurodevelopmental symptoms and in-session acute cortisol responses were also evaluated.ResultsNo significant between group differences were observed in cortisol responsiveness at week-1. By week-4, in-session changes in cortisol were evident, with significantly greater decreases in the AAI group (Cohen’s d = -.40). This pattern was also observed at week-8, with an even stronger effect-size (d = -0.60). Concurrent symptoms of autism were associated with the in-session acute cortisol response. Specifically, higher parent-reported symptom scores were associated with steeper decreases in cortisol across the session at week 1 (r = -0.42, p

Abstract The epidermal growth factor receptor, EGFR, is frequently activated in lung cancer and glioblastoma by genomic alterations including missense mutations. The different mutation spectra in these diseases are reflected in divergent responses to EGFR inhibition: significant patient benefit in lung cancer, but limited in glioblastoma. Here, we report a comprehensive mutational analysis of EGFR function. We perform saturation mutagenesis of EGFR and assess function of ~22,500 variants in a human EGFR-dependent lung cancer cell line. This approach reveals enrichment of erlotinib-insensitive variants of known and unknown significance in the dimerization, transmembrane, and kinase domains. Multiple EGFR extracellular domain variants, not associated with approved targeted therapies, are sensitive to afatinib and dacomitinib in vitro. Two glioblastoma patients with somatic EGFR G598V dimerization domain mutations show responses to dacomitinib treatment followed by within-pathway resistance mutation in one case. In summary, this comprehensive screen expands the landscape of functional EGFR variants and suggests broader clinical investigation of EGFR inhibition for cancers harboring extracellular domain mutations.

Objective Evaluate the association between cancer incidence and immunosuppressive treatment in patients with ocular inflammatory disease (OID).Methods and analysis We performed a retrospective cohort study of patients from 10 US OID subspecialty practices. Patients with non-infectious OID were included; HIV-infected patients were excluded. Time-dependent exposure to drug classes (ie, antimetabolites, calcineurin inhibitors, alkylating agents, tumour necrosis factor (TNF) inhibitors) and drugs were evaluated. Cancer incidence was ascertained by linkage to 12 state cancer registries from 1996 to 2015. Cancer incidence was analysed using Cox regression survival analysis, using 0-year, 3-year and 5-year lags after immunosuppression began.Results The cancer incidence cohort comprised 10 872 individuals at risk of incident cancer and residing in one of the 12 states covered; 812 primary cancers were identified through cancer incidence tracing with median follow-up time of 10 years. Neither TNF inhibitor, antimetabolite, calcineurin inhibitor nor alkylating agent classes were associated with statistically significant increases in cancer incidence adjusting for covariates. We found statistically significant reduced hazards in the systemic inflammatory disease (SID)-including cohort for adalimumab and chlorambucil, increased hazards for tacrolimus and etanercept in the non-SID cohort and reduced hazards for methotrexate in both. Other immunosuppressive drugs were not associated with overall cancer incidence.Conclusions We found no increased risk of overall or site-specific cancer incidence associated with short-term (non-transplant) therapy with most commonly used immunosuppressive drug classes and many specific drugs. Further research may clarify potentially protective or harmful effects of specific agents that were not consistently associated with reduced or increased cancer incidence.Trial registration number NCT00116090.

This study addresses the problem of shadows in multi-temporal imagery, which is a key issue with change detection approaches based on image comparison. We apply image-to-image radiometric normalizations including histogram matching (HM), mean-variance (MV) equalization, linear regression based on pseudo-invariant features (PIF-LR), and radiometric control sets (RCS) representing high- and low-reflectance extrema, for the novel purpose of normalizing brightness of transient shadows in high spatial resolution, bi-temporal, aerial frame image sets. Efficient shadow normalization is integral to remote sensing procedures that support disaster response efforts in a near-real-time fashion, including repeat station image (RSI) capture, wireless data transfer, shadow detection (as precursor to shadow normalization), and change detection based on image differencing and visual interpretation. We apply the normalization techniques to imagery of suburban scenes containing shadowed materials of varied spectral reflectance characteristics, whereby intensity (average of red, green, and blue spectral band values) under fully illuminated conditions is known from counterpart reference images (time-1 versus time-2). We evaluate the normalization results using stratified random pixel samples within transient shadows, considering central tendency and variance of differences in intensity relative to the unnormalized images. Overall, MV equalization yielded superior results in our tests, reducing the radiometric effects of shadowing by more than 85 percent. The HM and PIF-LR approaches showed slightly lower performance than MV, while the RCS approach proved unreliable among scenes and among stratified intensity levels. We qualitatively evaluate a shadow normalization based on MV equalization, describing its utility and limitations when applied in change detection. Application of image-to-image radiometric normalization for brightening shadowed areas in multi-temporal imagery in this study proved efficient and effective to support change detection.

Introduction: Children with Attention Deficit/Hyperactivity Disorder (ADHD) participated in a randomized clinical trial comparing animal-assisted intervention (AAI) to psychosocial treatment as usual (TAU). This brief report describes effects of AAI on acute HPA axis reactivity and regulation. Saliva was collected before, during, and after psychosocial intervention sessions with and without therapy dogs and later assayed for cortisol (ug/dL). Methodology: Thirty-nine participants (n = 39) with ADHD, aged 7-9 years (79% male) provided saliva at 3 points during 90-minute sessions; (i) upon arrival, (ii) +20 minutes, and (iii) 15 minutes prior to departure, on 3 occasions across an 8-week intervention (weeks 1, 4, and 8). Cortisol slopes calculated within each session were compared across the intervention weeks to determine within subject and between group effect sizes. Spearman's correlations between baseline individual neurodevelopmental symptoms and in-session acute cortisol responses were also evaluated. Results: No significant between group differences were observed in cortisol responsiveness at week-1. By week-4, in-session changes in cortisol were evident, with significantly greater decreases in the AAI group (Cohen's d = -.40). This pattern was also observed at week-8, with an even stronger effect-size (d = -0.60). Concurrent symptoms of autism were associated with the in-session acute cortisol response. Specifically, higher parent-reported symptom scores were associated with steeper decreases in cortisol across the session at week 1 (r = -0.42, p <.01) and week-8 (r = -0.34 p =.05). At week-8 this association was stronger in the AAI group (r = -0.53) versus TAU (r = -0.25), with Cohen's q = 0.413). Discussion: AAI may influence acute HPA reactivity and regulation for children with ADHD. Concurrent symptoms of ADHD and autism may be related to individual differences in the nature of the effect. Implications of these findings for AAI as an alternative, or complementary intervention for ADHD are discussed. Clinical trial registration: ClinicalTrials.gov, identifier NCT05102344. [ABSTRACT FROM AUTHOR]

Byline: Alan V. Douglas (1) Keywords: Managerial Information Advantages; Endogenous Objective Functions; Financial Commit-ments; Agency Costs; Dividend Puzzle Abstract: This paper studies the optimal combination of debt and dividend commitmentsin an agency model of the firm. Financial policy is relevant because ex-post information asymmetry requires managerial rewards to depend on the ability to meet financial commitments. If perquisite or inside information problems exist in isolation, debt-based incentives as assumed in previous studies result endogenously. If the problems exist simultaneously, dividends can be optimal even when they appear excessively costly as a signal and unduly lenient as a disciplining device. The reason is that the set of dynamically consistent rewards increases when debt commitments are augmented with dividend commitments, and a larger set of ex-post rewards is more valuable as ex-antedecisions become more complex. Author Affiliation: (1) School of Accountancy, Centre for Advanced Studies in Finance, University of Waterloo, Waterloo, Ontario, Canada, N2L 3G1 Article History: Registration Date: 10/10/2004

Research was conducted to confirm anti-methicillin-resistant Staphylococcus aureus activity on carbapenems, specifically L-742,728, having aromatic substituents at the 3-position. The study utilized the Suzuki-Miyaura crosscoupling between dicationic boronic acid 20 and in situ prepared carbapenem vinyl triflate 26 as the key reaction. Results indicated synthesis of the carbapenem in 31-36% yield over six steps from the diazo intermediate 2.

A chromatography-free method of preparing a fibrinogen receptor antagonist, the non-peptide L-734,217, is introduced. It requires the generation of a chiral pyridine acid intermediate via the silyl-mediated conjugate addition of ethyl (2-oxopiperidin-1-yl)acetate to 4-vinylpyridine. The acid undergoes peptide coupling with benzyl beta-aminobutyrate. After this, pyridine is hydrogenated to piperidene while debenzylation takes place.