Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non–Small Cell Lung Cancer: A Phase Ib Study

Purpose: Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated preclinical activity in non–small cell lung cancer (NSCLC). A multicenter, nonrandomized, open-label phase Ib study was conducted to test safety, MTD, pharmacokinetics, and preliminary antitumor activity of abemaciclib in combination with other therapies for treatment in patients with metastatic NSCLC. Patients and Methods: An initial dose escalation phase was used to determine the MTD of twice-daily oral abemaciclib (150, 200 mg) plus pemetrexed, gemcitabine, or ramucirumab, followed by an expansion phase for each drug combination. Pemetrexed and gemcitabine were administered according to label. The abemaciclib plus ramucirumab study examined two dosing schedules. Results: The three study parts enrolled 86 patients; all received ≥1 dose of combination therapy. Across arms, the most common treatment-emergent adverse events were fatigue, diarrhea, neutropenia, decreased appetite, and nausea. The trial did not identify an abemaciclib MTD for the combination with pemetrexed or gemcitabine but did so for the combination of abemaciclib with days 1 and 8 ramucirumab (8 mg/kg). Plasma sample analysis showed that abemaciclib did not influence the pharmacokinetics of the combination agents and the combination agents did not affect abemaciclib exposure. The disease control rate was 57% for patients treated with abemaciclib–pemetrexed, 25% for abemaciclib–gemcitabine, and 54% for abemaciclib–ramucirumab. Median progression-free survival was 5.55, 1.58, and 4.83 months, respectively. Conclusions: Abemaciclib demonstrated an acceptable safety profile when dosed on a continuous twice-daily schedule in combination with pemetrexed, gemcitabine, or ramucirumab. Abemaciclib exposures remained consistent with those observed in single-agent studies

Differences in Gut Microbiome in Hospitalized Immunocompetent vs. Immunocompromised Children, Including Those With Sickle Cell Disease.

Background: Gut microbial diversity and composition play important roles in health. This cross-sectional study was designed to test the hypothesis that hospitalized children who may be relatively immunocompromised (IC), defined as those with cancer, sickle cell disease (SCD), transplantation, or receiving immunosuppressive therapy) would have decreased microbial diversity, increased Clostridioides difficile colonization and different species composition compared to non-immunocompromised (Non-IC) children admitted to the same pediatric unit. Methods: A stool sample was obtained within 72 h of admission to a single unit at The Children\u27s Hospital at Montefiore, Bronx, NY from March 2016 to February 2017 and the microbiome assessed by 16S rRNA sequencing. C. difficile colonization was assessed by glutamate dehydrogenase antigen and toxin polymerase chain reaction assays. Results: Stool samples were obtained from 69 IC (32 SCD, 19 cancer, 9 transplantation and 9 other) and 37 Non-IC patients. There were no significant differences in microbial alpha diversity and C. difficile colonization comparing IC vs. non-IC patients. Lower alpha diversity, however, was independently associated with the use of proton pump inhibitors or antibiotics, including prophylactic penicillin in patients with SCD. Differences in specific species abundances were observed when comparing IC vs. non-IC patients, particularly children with SCD. Non-IC patients had increased abundance of commensals associated with health including Alistipes putredinis, Alistipes ihumii, Roseburia inulinivorans, Roseburia intestinalis, and Ruminococcus albus (p \u3c 0.005). Conclusions: Antibiotics and proton pump inhibitors, which were more commonly used in IC children, were identified as risk factors for lower microbial diversity. Non-IC patients had higher abundance of several bacterial species associated with health. Longitudinal studies are needed to determine the clinical significance of these differences in gut microbiome

Nature as capital: Advancing and incorporating ecosystem services in United States federal policies and programs

The concept of nature as capital is gaining visibility in policies and practices in both the public and private sectors. This change is due to an improved ability to assess and value ecosystem services, as well as to a growing recognition of the potential of an ecosystem services approach to make tradeoffs in decision making more transparent, inform efficient use of resources, enhance resilience and sustainability, and avoid unintended negative consequences of policy actions. Globally, governments, financial institutions, and corporations have begun to incorporate natural capital accounting in their policies and practices. In the United States, universities, nongovernmental organizations, and federal agencies are actively collaborating to develop and apply ecosystem services concepts to further national environmental and economic objectives. Numerous federal agencies have begun incorporating these concepts into land use planning, water resources management, and preparations for, and responses to, climate change. Going forward, well-defined policy direction will be necessary to institutionalize ecosystem services approaches in federal agencies, as well as to guide intersector and interdisciplinary collaborative research and development efforts. In addition, a new generation of decision support tools are needed to further the practical application of ecosystem services principles in policymaking and commercial activities. Improved performance metrics are needed, as are mechanisms to monitor the status of ecosystem services and assess the environmental and economic impacts of policies and programs. A greater national and international financial commitment to advancing ecosystem services and natural capital accounting would likely have broad, long-term economic and environmental benefits.Keywords: US federal agencies, environmental policy, natural capital, ecosystem service

Peer mentoring for smoking cessation in public housing: A mixed-methods study

IntroductionTobacco use disproportionately affects low-income African American communities. The recent public housing smoke-free policy has increased the demand for effective smoking cessation services and programs in such settings.MethodsThis mixed-method pilot study explored feasibility and potential impact of a peer-mentoring program for smoking cessation in a public housing unit. The quantitative study used a quasi-experimental design while qualitative data were collected via focus group discussions with peer mentors and participants. Three residents of the public housing complex were trained as peer mentors. Each peer mentor recruited up to 10 smokers in the residence and provided them individual support for 12 weeks. All participants were offered Nicotine Replacement Therapy (NRT). A follow-up investigation was conducted 3 months after completion of the 12-week intervention. At baseline and follow-up, the participants' smoking status was measured using self-report and was verified using exhaled carbon monoxide (eCO) monitoring.ResultsThe intervention group was composed of 30 current smokers who received the peer-mentoring intervention. The control group was composed of 14 individuals. Overall mean eCO levels dropped from 26 ppm (SD 19.0) at baseline to 12 (SD 6.0) at follow-up (P < 0.01). Participants who were enrolled in our program were more likely to have non-smoking eCO levels (<7 ppm) at follow-up (23.3%) compared to those who did not enroll (14.3%).ConclusionOur program is feasible for low-income predominantly African American communities. Using peers as mentors may be helpful in providing services for hard-to-reach populations. Given the non-randomized design of our study, randomized trials are needed to test the efficacy of our program in the future

Political Self-characterization of U.S. Medical Students

BACKGROUND: There have been no prior studies of the political self-characterization of U.S. physicians-in-training, and little is known about physicians’ political leanings or the critical relationship between medical issues and political orientations of physicians and physicians-in-training. METHODS: All medical students in the class of 2003 at 16 nationally representative U.S. schools were eligible to complete three questionnaire administrations (at freshman orientation, entrance to wards, and senior year). RESULTS: Among these medical students, 5% self-characterized as politically very conservative, 21% conservative, 33% moderate, 31% liberal, and 9% as very liberal.” Being male, white, Protestant, intending to specialize in Surgery or anesthesiology/pathology/radiology, or currently or previously being married significantly (P ≤ .001) increased the likelihood that a student self-identified as very conservative or conservative. Disagreement or strong disagreement with the statements, “I’m glad I chose to become a physician” and “Access to care is a fundamental human right,” were also both associated with being very conservative or conservative. Being more liberal was reported by blacks and Hispanics; those intending to become ob-gyns, psychiatrists, and pediatric subspecialists; and atheists, Jews, and adherents of eastern religions. CONCLUSIONS: U.S. medical students are considerably more likely to be liberal than conservative and are more likely to be liberal than are other young U.S. adults. Future U.S. physicians may be more receptive to liberal messages than conservative ones, and their political orientation may profoundly affect their health system attitudes

Addictions NeuroImaging Assessment (ANIA): Towards an integrative framework for alcohol use disorder.

Alcohol misuse and addiction are major international public health issues. Addiction can be characterized as a disorder of aberrant neurocircuitry interacting with environmental, genetic and social factors. Neuroimaging in alcohol misuse can thus provide a critical window into underlying neural mechanisms, highlighting possible treatment targets and acting as clinical biomarkers for predicting risk and treatment outcomes. This neuroimaging review on alcohol misuse in humans follows the Addictions Neuroclinical Assessment (ANA) that proposes incorporating three functional neuroscience domains integral to the neurocircuitry of addiction: incentive salience and habits, negative emotional states, and executive function within the context of the addiction cycle. Here we review and integrate multiple imaging modalities focusing on underlying cognitive processes such as reward anticipation, negative emotionality, cue reactivity, impulsivity, compulsivity and executive function. We highlight limitations in the literature and propose a model forward in the use of neuroimaging as a tool to understanding underlying mechanisms and potential clinical applicability for phenotyping of heterogeneity and predicting risk and treatment outcomes

Development of a Measure to Inform Return-to-Duty Decision Making After Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI), a principal injury of the wars in Iraq and Afghanistan, can result in significant morbidity. To make accurate return-to-duty decisions for soldiers with mTBI, military medical personnel require sensitive, objective, and duty-relevant data to characterize subtle cognitive and sensorimotor injury sequelae. A military-civilian research team reviewed existing literature and obtained input from stakeholders, end users, and experts to specify the concept and develop a preliminary assessment protocol to address this need. Results of the literature review suggested the potential utility of a test based on dual-task and multitask assessment methods. Thirty-three individuals representing a variety of military and civilian stakeholders/experts participated in interviews. Interview data suggested that reliability/validity, clinical feasibility, usability across treatment facilities, military face validity, and capacity to challenge mission-critical mTBI vulnerabilities were important to ultimate adoption. The research team developed the Assessment of Military Multitasking Performance, a tool composed of eight dual and multitasking test-tasks. A concept test session with 10 subjects indicated preliminary face validity and informed modifications to scoring and design. Further validation is needed. The Assessment of Military Multitasking Performance may fill a gap identified by stakeholders for complex cognitive/motor testing to assist return-to-duty decisions for service members with mTBI

Ten Years In: Implementing Strategic Approaches to Cyberspace

This book represents a look beyond theories and analogies to examine the challenges of strategy implementation. In the essays that follow, practitioners who are building cyberspace forces at-scale join scholars who study power and force in this new domain to collectively offer a unique perspective on the evolution and future of cyber strategy and operations.https://digital-commons.usnwc.edu/usnwc-newport-papers/1044/thumbnail.jp

A SMART decade: outcomes of an integrated, inclusive, first-year college-level STEM curricular innovation

In the early 2000s, our primarily undergraduate, white institution (PUI/PWI), began recruiting and enrolling higher numbers of students of color and first-generation college students. However, like many of our peer institutions, our established pedagogies and mindsets did not provide these students an educational experience to enable them to persist and thrive in STEM. Realizing the need to systematically address our lack of inclusivity in science majors, in 2012 faculty from multiple disciplines developed the Science, Math, and Research Training (SMART) program. Here, we describe an educational innovation, originally funded by a grant from the Howard Hughes Medical Institute, designed to support and retain students of color, first generation college students, and other students with marginalized identities in the sciences through a cohort-based, integrated, and inclusive first-year experience focused on community and sense of belonging. The SMART program engages first-year students with semester-long themed courses around “real world” problems of antibiotic resistance and viral infections while integrating the fields of Biology, Chemistry, Mathematics, and an optional Computer Science component. In the decade since its inception, 97% of SMART students have graduated or are on track to graduate, with 80.9% of these students earning a major in a STEM discipline. Here, we present additional student outcomes since the initiation of this program, results of the student self-evaluative surveys SALG and CURE, and lessons we have learned from a decade of this educational experience