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Many advances in health care fail to reach patients. Implementation science is the study of novel approaches to mitigate this evidence-to-practice gap.The American Thoracic Society (ATS) created a multidisciplinary ad hoc committee to develop a research statement on implementation science in pulmonary, critical care, and sleep medicine. The committee used an iterative consensus process to define implementation science and review the use of conceptual frameworks to guide implementation science for the pulmonary, critical care, and sleep community and to explore how professional medical societies such as the ATS can promote implementation science.The committee defined implementation science as the study of the mechanisms by which effective health care interventions are either adopted or not adopted in clinical and community settings. The committee also distinguished implementation science from the act of implementation. Ideally, implementation science should include early and continuous stakeholder involvement and the use of conceptual frameworks (i.e., models to systematize the conduct of studies and standardize the communication of findings). Multiple conceptual frameworks are available, and we suggest the selection of one or more frameworks on the basis of the specific research question and setting. Professional medical societies such as the ATS can have an important role in promoting implementation science. Recommendations for professional societies to consider include: unifying implementation science activities through a single organizational structure, linking front-line clinicians with implementation scientists, seeking collaborations to prioritize and conduct implementation science studies, supporting implementation science projects through funding opportunities, working with research funding bodies to set the research agenda in the field, collaborating with external bodies responsible for health care delivery, disseminating results of implementation science through scientific journals and conferences, and teaching the next generation about implementation science through courses and other media.Implementation science plays an increasingly important role in health care. Through support of implementation science, the ATS and other professional medical societies can work with other stakeholders to lead this effort.

More than 1.5 million adults in the United States use supplemental oxygen for a variety of respiratory disorders to improve their quality of life and prolong survival. This document describes recommendations from a multidisciplinary workshop convened at the ATS International Conference in 2017 with the goal of optimizing home oxygen therapy for adults. Ideal supplemental oxygen therapy is patient-specific, provided by a qualified clinician, includes an individualized prescription and therapeutic education program, and offers oxygen systems that are safe, promote mobility, and treat hypoxemia. Recently, patients and clinicians report a growing number of problems with home oxygen in the United States. Oxygen users experience significant functional, mechanical, and financial problems and a lack of education related to their oxygen equipment-problems that impact their quality of life. Health care providers report a lack of readily accessible resources needed to prescribe oxygen systems correctly and efficiently. Patients with certain lung diseases are affected more than others because of physically unmanageable or inadequate portable systems. Analysis is needed to quantify the unintended impact that the Centers for Medicare and Medicaid Services Competitive Bidding Program has had on patients receiving supplemental oxygen from durable medical equipment providers. Studies using effectiveness and implementation research designs are needed to develop and evaluate new models for patient education, identify effective ways for stakeholders to interface, determine the economic benefit of having respiratory therapists perform in-home education and follow-up testing, and collaborate with technology companies to improve portable oxygen devices. Generation of additional evidence of the benefit of supplemental oxygen across the spectrum of advanced lung diseases and the development of clinical practice guidelines should both be prioritized.

Active-learning pedagogies have been repeatedly demonstrated to produce superior learning gains with large effect sizes compared with lecture-based pedagogies. Shifting large numbers of college science, technology, engineering, and mathematics (STEM) faculty to include any active learning in their teaching may retain and more effectively educate far more students than having a few faculty completely transform their teaching, but the extent to which STEM faculty are changing their teaching methods is unclear. Here, we describe the development and application of the machine-learning-derived algorithm Decibel Analysis for Research in Teaching (DART), which can analyze thousands of hours of STEM course audio recordings quickly, with minimal costs, and without need for human observers. DART analyzes the volume and variance of classroom recordings to predict the quantity of time spent on single voice (e.g., lecture), multiple voice (e.g., pair discussion), and no voice (e.g., clicker question thinking) activities. Applying DART to 1,486 recordings of class sessions from 67 courses, a total of 1,720 h of audio, revealed varied patterns of lecture (single voice) and nonlecture activity (multiple and no voice) use. We also found that there was significantly more use of multiple and no voice strategies in courses for STEM majors compared with courses for non-STEM majors, indicating that DART can be used to compare teaching strategies in different types of courses. Therefore, DART has the potential to systematically inventory the presence of active learning with ∼90% accuracy across thousands of courses in diverse settings with minimal effort.

Instructor Talk—noncontent language used by instructors in classrooms—is a recently defined and promising variable for better understanding classroom dynamics. Having previously characterized the Instructor Talk framework within the context of a single course, we present here our results surrounding the applicability of the Instructor Talk framework to noncontent language used by instructors in novel course contexts. We analyzed Instructor Talk in eight additional biology courses in their entirety and in 61 biology courses using an emergent sampling strategy. We observed widespread use of Instructor Talk with variation in the amount and category type used. The vast majority of Instructor Talk could be characterized using the originally published Instructor Talk framework, suggesting the robustness of this framework. Additionally, a new form of Instructor Talk—Negatively Phrased Instructor Talk, language that may discourage students or distract from the learning process—was detected in these novel course contexts. Finally, the emergent sampling strategy described here may allow investigation of Instructor Talk in even larger numbers of courses across institutions and disciplines. Given its widespread use, potential influence on students in learning environments, and ability to be sampled, Instructor Talk may be a key variable to consider in future research on teaching and learning in higher education.

Withanolide E (WE), a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to TRAIL-mediated apoptosis. WE, the most potent and least toxic of 5 TRAIL sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling via a rapid decline in the levels of both cFLIPL and cFLIPS proteins. Normal non-transformed human renal epithelial cells were completely resistant to the WE plus TRAIL combination. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in various pro-and anti-apoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIPL and cFLIPS was predominantly due to destabilization and/or aggregation of the proteins subsequently leading to their proteasomal degradation. Since cFLIPL and cFLIPS are reported to be HSP90 client proteins, and WE can inhibit HSP90 activity, the effect of WE on various other HSP90 client proteins was assessed. WE treatment of ACHN renal carcinoma cells altered the stability of a limited number of HSP90 client proteins when compared to the well-known HSP90 inhibitor geldanamycin. The destabilization of cFLIP proteins provides a potentially novel mechanism for sensitizing cancer cells to TRAIL mediated apoptosis. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by WE and its lack of toxicity were confirmed in animal studies, in which a combination treatment of WE with an agonist antibody to TRAIL death receptor 5 (DR5) provided a significant therapeutic benefit compared to either agent alone in a renal cancer xenograft model. Due to its novel activity, WE is a promising reagent for analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. Various structural analogs of WE are currently being tested for their TRAIL-sensitizing activity to provide more insight into Structure Activity Relationships (SAR) for these compounds. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, WE's more specific mechanism of action suggests minimal toxic side effects might accompany its combination with TRAIL death receptor agonists for cancer therapy. Citation Format: Brooks D. Alan, Curtis J. Henrich, Karen L. Erickson, Cheryl L. Thomas, Heidi R. Bokesch, Poonam Tewary, Candace R. Thompson, Richard J. Pompei, Kirk R. Gustafson, James B. McMahon, Thomas J. Sayers. Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2928. doi:10.1158/1538-7445.AM2015-2928