Outcomes of Physicians' Communication Goals During Patient Interactions.

During healthcare visits, physicians may set communication goals such as providing their patient with information about treatment; however, no recommendations exist regarding which goals physicians should prioritize during their often-brief interactions with patients. Two studies examined five communication goals (providing information, reducing distress, increasing patient satisfaction, increasing patient adherence, and encouraging hope) in the context of physician-patient interactions and their relationship with patient and physician outcomes. In Study 1, audio-recordings of physician-patient interactions were coded by research assistants for goal-related content. In Study 2, patients reported their physician's use of each goal during the interaction. In both studies, patients and physicians reported visit outcomes. Within-study meta-analyses suggested that the goal of reducing distress, but not the other goals, was consistently related to improved outcomes in Study 1. All goals were related to improved outcomes in Study 2. We then computed sample-size-weighted meta-analytic effects of each goal on each outcome across both studies. These results suggested that all of the goals had similar-sized positive relationships with patient and physician outcomes across studies. These findings suggest that physicians should generally approach consultations with communication goals in mind, but prioritizing efforts to reduce distress may be particularly beneficial

Novel cell adhesion/migration pathways are predictive markers of HDAC inhibitor resistance in cutaneous T cell lymphoma

BACKGROUND: Treatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting therapy that is effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the CTCL histone acetylation landscape remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy. METHODS: Purified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks (H3K14/9 ac, H3K27ac). We correlated significant differences in histone acetylation with gene expression in HDACi-resistant/sensitive CTCL. We extended these findings in additional CTCL patient cohorts (RNA-seq, microarray) and using ELISA in matched CTCL patient plasma. FINDINGS: Resistant CTCL exhibited high levels of histone acetylation, which correlated with increased expression of 338 genes (FDR \u3c 0·05), including some novel to CTCL: BIRC5 (anti-apoptotic); RRM2 (cell cycle); TXNDC5, GSTM1 (redox); and CXCR4, LAIR2 (cell adhesion/migration). Several of these, including LAIR2, were elevated pre-treatment in HDACi-resistant CTCL. In CTCL patient plasma (n = 6), LAIR2 protein was also elevated (p \u3c 0·01) compared to controls. INTERPRETATION: This study is the first to connect genome-wide differences in chromatin acetylation and gene expression to HDACi-resistance in primary CTCL. Our results identify novel markers with high pre-treatment expression, such as LAIR2, as potential prognostic and/or predictors of HDACi-resistance in CTCL. FUNDING: NIH:CA156690, CA188286; NCATS: WU-ICTS UL1 TR000448; Siteman Cancer Center: CA091842

Reporting Contingencies: Environmental Liabilities

The dawn of environmental regulation in the late 1960’s and its proliferation through the early 1980’s resulted in a new regulatory climate for business and increased potential contingent liabilities. Recent efforts toward convergence with international accounting standards increase disclosure and improve transparency for decision makers but also impact financial reporting. This article uses a case study set in the context of potential liability under the federal Comprehensive Environmental Response Compensation and Liability Act of 1980 (CERCLA) to illustrate financial reporting with respect to uncertain environmental liabilities under current and proposed requirements of Financial Accounting Standard 5 Accounting for Contingencies (SFAS 5), now known as Accounting Standards Update 450 (ASU 450). Financial reporting under the proposed requirements provides increased transparency for users and more complete information upon which to make decisions

Protective actions of des-acylated ghrelin on brain injury and blood-brain barrier disruption after stroke in mice

The major ghrelin forms, acylated ghrelin and des-acylated ghrelin, are novel gastrointestinal hormones. Moreover, emerging evidence indicates that these peptides may have other functions including neuro- and vaso-protection. Here, we investigated whether post-stroke treatment with acylated ghrelin or des-acylated ghrelin could improve functional and histological endpoints of stroke outcome in mice after transient middle cerebral artery occlusion (tMCAo). We found that des-acylated ghrelin (1 mg/kg) improved neurological and functional performance, reduced infarct and swelling, and decreased apoptosis. In addition, it reduced blood-brain barrier (BBB) disruption in vivo and attenuated the hyper-permeability of mouse cerebral microvascular endothelial cells after oxygen glucose deprivation and reoxygenation (OGD + RO). By contrast, acylated ghrelin (1 mg/kg or 5 mg/kg) had no significant effect on these endpoints of stroke outcome. Next we found that des-acylated ghrelin's vasoprotective actions were associated with increased expression of tight junction proteins (occludin and claudin-5), and decreased cell death. Moreover, it attenuated superoxide production, Nox activity and expression of 3-nitrotyrosine. Collectively, these results demonstrate that post-stroke treatment with des-acylated ghrelin, but not acylated ghrelin, protects against ischaemia/reperfusion-induced brain injury and swelling, and BBB disruption, by reducing oxidative and/or nitrosative damage

The Smart Airport App, Transit.io: The Travel Optimizer

Jacqueline Andrews, Devin Burke, Uvika Chaturvedi, Jake Collins, Pranav Gupta, Vikrant Neb, Harsh Somani, and Alyssa Williams were all seniors in industrial engineering in the spring semester of 2016. They were members of Team 3 in the course titled Human Factors and Work Analysis (IE 486). This course explores the application of engineering, computer sciences, information sciences, and psychological principles and methods to the analysis and design of human work systems. In this article, the students describe their development of an application prototype to improve the airport travel experience

Determining subpopulation methylation profiles from bisulfite sequencing data of heterogeneous samples using DXM

Epigenetic changes, such as aberrant DNA methylation, contribute to cancer clonal expansion and disease progression. However, identifying subpopulation-level changes in a heterogeneous sample remains challenging. Thus, we have developed a computational approach, DXM, to deconvolve the methylation profiles of major allelic subpopulations from the bisulfite sequencing data of a heterogeneous sample. DXM does not require prior knowledge of the number of subpopulations or types of cells to expect. We benchmark DXM\u27s performance and demonstrate improvement over existing methods. We further experimentally validate DXM predicted allelic subpopulation-methylation profiles in four Diffuse Large B-Cell Lymphomas (DLBCLs). Lastly, as proof-of-concept, we apply DXM to a cohort of 31 DLBCLs and relate allelic subpopulation methylation profiles to relapse. We thus demonstrate that DXM can robustly find allelic subpopulation methylation profiles that may contribute to disease progression using bisulfite sequencing data of any heterogeneous sample

Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription

Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV

Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease

Jacqeline Bayliss, Romana Stark, Moyra Lemus, Vanessa Santos, Aiysha Thompson, Daniel Rees, Sandra Galic, John Elsworth, Bruce Kemp, Jeffrey Davies, and Zane Andrew