Recommendations for Effective Integration of Ethics and Responsible Conduct of Research (E/RCR) Education into Course-Based Undergraduate Research Experiences: A Meeting Report.

Advancement of the scientific enterprise relies on individuals conducting research in an ethical and responsible manner. Educating emergent scholars in the principles of ethics/responsible conduct of research (E/RCR) is therefore critical to ensuring such advancement. The recent impetus to include authentic research opportunities as part of the undergraduate curriculum, via course-based undergraduate research experiences (CUREs), has been shown to increase cognitive and noncognitive student outcomes.

Collaborative Posters Develop Students' Ability to Communicate about Undervalued Scientific Resources to Nonscientists.

Scientists are increasingly called upon to communicate with the public, yet most never receive formal training in this area. Public understanding is particularly critical to maintaining support for undervalued resources such as biological collections, research data repositories, and expensive equipment. We describe activities carried out in an inquiry-driven organismal biology laboratory course designed to engage a diverse student body using biological collections.

Burden of Psychosocial and Cognitive Impairment in Patients With Atrial Fibrillation.

Background: Impairments in psychosocial status and cognition relate to poor clinical outcomes in patients with atrial fibrillation (AF). However, how often these conditions co-occur and associations between burden of psychosocial and cognitive impairment and quality of life (QoL) have not been systematically examined in patients with AF.

Methods: A total of 218 patients with symptomatic AF were enrolled in a prospective study of AF and psychosocial factors between May 2013 and October 2014 at the University of Massachusetts Medical Center.

Association of Left Atrial Function Index With Late Atrial Fibrillation Recurrence after Catheter Ablation.

Introduction: Although catheter ablation (CA) for atrial fibrillation (AF) is commonly used to improve symptoms, AF recurrence is common and new tools are needed to better inform patient selection for CA. Left atrial function index (LAFI), an echocardiographic measure of atrial mechanical function, has shown promise as a noninvasive predictor of AF. We hypothesized that LAFI would relate to AF recurrence after CA.

Relation of Atrial Fibrillation in Acute Myocardial Infarction to In-Hospital Complications and Early Hospital Readmission.

Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI) and contributes to high rates of in-hospital adverse events. However, there are few contemporary studies examining rates of AF in the contemporary era of AMI or the impact of new-onset AF on key in-hospital and postdischarge outcomes. We examined trends in AF in 6,384 residents of Worcester, Massachusetts, who were hospitalized with confirmed AMI during 7 biennial periods between 1999 and 2011.

Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation.

Introduction: Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores.

PULSE-SMART: Pulse-Based Arrhythmia Discrimination Using a Novel Smartphone Application.

Background: Atrial fibrillation (AF) is a common and dangerous rhythm abnormality. Smartphones are increasingly used for mobile health applications by older patients at risk for AF and may be useful for AF screening.

Objectives: To test whether an enhanced smartphone app for AF detection can discriminate between sinus rhythm (SR), AF, premature atrial contractions (PACs), and premature ventricular contractions (PVCs).

OX40 is a potent immune-stimulating target in late-stage cancer patients.

OX40 is a potent costimulatory receptor that can potentiate T-cell receptor signaling on the surface of T lymphocytes, leading to their activation by a specifically recognized antigen. In particular, OX40 engagement by ligands present on dendritic cells dramatically increases the proliferation, effector function, and survival of T cells. Preclinical studies have shown that OX40 agonists increase antitumor immunity and improve tumor-free survival.

Dual anti-OX40/IL-2 therapy augments tumor immunotherapy via IL-2R-mediated regulation of OX40 expression.

The provision of T cell co-stimulation via members of the TNFR super-family, including OX40 (CD134) and 4-1BB (CD137), provides critical signals that promote T cell survival and differentiation. Recent studies have demonstrated that ligation of OX40 can augment T cell-mediated anti-tumor immunity in pre-clinical models and more importantly, OX40 agonists are under clinical development for cancer immunotherapy. OX40 is of particular interest as a therapeutic target as it is not expressed on naïve T cells but rather, is transiently up-regulated following TCR stimulation.

A 30-year perspective (1975-2005) into the changing landscape of patients hospitalized with initial acute myocardial infarction: Worcester Heart Attack Study.

Background: The effects of lifestyle changes and evolving treatment practices on coronary disease incidence rates, demographic and clinical profile, and the short-term outcomes of patients hospitalized with acute myocardial infarction have not been well characterized. The purpose of this study was to examine multidecade-long trends (1975-2005) in the incidence rates, demographic and clinical characteristics, treatment practices, and hospital outcomes of patients hospitalized with an initial acute myocardial infarction from a population-based perspective.

Methods And Results: Residents of the Worcester, Mass, metropolitan area (median age, 37 years; 89% white) hospitalized with an initial acute myocardial infarction (n=8898) at all greater-Worcester medical centers during 15 annual periods between 1975 and 2005 comprised the sample of interest.

Classification and atherosclerosis distribution in patients with left main coronary disease.

Objective: The purpose of this investigation was to characterize clinical variables and angiographic distribution of coronary atherosclerosis to classify patients with de novo left main (LM) disease in a real-world population presenting for coronary angiography.

Background: Limited quantitative and angiographic published data exist that provide detailed quantitative information to classify potential target population for elective LM percutaneous coronary intervention (PCI) and guide development of dedicated LM PCI platforms.

Methods: Medical history and clinical presentation were prospectively collected on 177 consecutive patients with LM stenosis > or =50% by coronary angiography.

Characterization of the class I-restricted gp100 melanoma peptide-stimulated primary immune response in tumor-free vaccine-draining lymph nodes and peripheral blood.

Purpose: The aim of this study was to characterize the primary gp100(209-2M)-specific T-cell response in vaccine-draining, metastases-free lymph nodes and peripheral blood of peptide-vaccinated stage I to III melanoma patients.

Experimental Design: After two or three gp100(209-2M) vaccinations, sentinel lymph nodes that drained both the primary tumor and adjacent vaccine sites were excised concomitant with wide excision of the tumor. Comparative 7-color flow cytometry phenotype analysis was done on gp100 tetramer-positive CD8(+) T cells from sentinel lymph nodes, closely proximate time-related peripheral blood mononuclear cells (PBMC) collected 2 to 4 weeks after sentinel lymph node excision, and on PBMC collected 6 months later after 7 or 11 more immunizations.

Phenotype and functional characterization of long-term gp100-specific memory CD8+ T cells in disease-free melanoma patients before and after boosting immunization.

Purpose: Effective cancer vaccines must both drive a strong CTL response and sustain long-term memory T cells capable of rapid recall responses to tumor antigens. We sought to characterize the phenotype and function of gp100 peptide-specific memory CD8+ T cells in melanoma patients after primary gp100(209-2M) immunization and assess the anamnestic response to boosting immunization.

Experimental Design: Eight-color flow cytometry analysis of gp100-specific CD8+ T cells was done on peripheral blood mononuclear cells collected shortly after the primary vaccine regimen, 12 to 24 months after primary vaccination, and after boosting immunization.

Polychromatic flow cytometry: a rapid method for the reduction and analysis of complex multiparameter data.

Background: Recent advances in flow cytometry have resulted in the development of reliable techniques for performing polychromatic (5-17 color) flow cytometry analysis. However, the data reduction and analysis involved in the resolution of hundreds of possible cellular subphenotypes identified, using a single polychromatic flow cytometry staining panel, presents a major obstacle to the successful application of this technology.

Methods: To generate two distinct collections of T cell populations with differentially expressed surface markers, cryopreserved lymph node cells from 5 melanoma patients vaccinated with the modified gp100(209-2M) melanoma peptide were stimulated with cognate peptide and cultured in either IL-21 + low-dose IL-2 or IL-15 + low-dose IL-2.

Age-based differences of percutaneous coronary intervention in the drug-eluting stent era.

Introduction: Limited data are available on contemporary percutaneous coronary intervention (PCI) practice patterns and outcomes in elderly patients. The objective of this study was to evaluate "real-world" PCI in elderly and nonelderly patients during the first year of availability of drug-eluting stents (DES) in the United States market (May 1, 2003-April 30, 2004).

Methods: One thousand one hundred sixty-six consecutive patients (272 elderly [age > or =75 years] and 894 nonelderly [age <75 years]) having PCI for de novo coronary artery disease (CAD) at Dartmouth-Hitchcock Medical Center were included in this study.

gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells.

Thirty-five HLA-A2(+) patients with completely resected stage I-III melanoma were vaccinated multiple times over 6 months with a modified melanoma peptide, gp100(209-2M), emulsified in Montanide adjuvant. Direct ex vivo gp100(209-2M) tetramer analysis of pre- and postvaccine peripheral blood mononuclear cells (PBMCs) demonstrated significant increases in the frequency of tetramer(+) CD8(+) T cells after immunization for 33 of 35 evaluable patients (median, 0.36%; range, 0.

Immunological monitoring of patients with melanoma after peptide vaccination using soluble peptide/HLA-A2 dimer complexes.

To facilitate the immunologic monitoring of a peptide vaccine trial, a novel, empty dimeric HLA-A2 molecule (A2 dimer) that could be loaded with peptides was produced. The dimer comprises the extracellular domain of HLA-A2 noncovalently linked to a fusion protein consisting of human beta2-microglobulin joined to the human IgG1 Fc domain. Peptide-loaded dimer complexes were used to assess the function of peptide-specific T cells.

Adaptation of commercial immunoassays to analysis of complex biological substances.

An Intracellular Adhesion Molecule I (ICAM-1) immunoassay from R and D Systems, and a Melanoma Inhibitory Activity (MIA) immunoassay from Roche Diagnostics were tested for accurate quantitation within complex biological substances such as cell lysates. Prior to assay, lysates of melanoma cells were treated with detergents to obtain soluble antigens. Maximum ICAM-1 and maximum MIA were detected after treatment using 0.