Stress, Physical Activity, and Resilience Resources: Tests of Direct and Moderation Effects in Young Adults

Stress is an important consideration for understanding why individuals take part in limited or no physical activity (PA). The effects of stress on PA do not hold for everyone, so examinations of possible moderators that protect individuals from the harmful effects of stress are required. Aligned with a resilience framework, individual resources (e.g., hope and self-efficacy) may buffer the maladaptive effects of stress, such that people who have access to these resources in greater quantity may be more "resilient" to the deleterious effects of stress on PA. This study was designed to test this expectation. In total, 140 Australian undergraduate students (70.7% female, Mage = 21.68 ± 4.88) completed a multisection survey and provided a sample for hair cortisol concentration analysis using immunoassays. Main effects demonstrated primarily small and nonsignificant associations between perceived stress and hair cortisol concentration with different intensities of PA. Similar findings were observed between individual-level resilience resources and PA intensities, with the exception of hope (i.e., positive association with vigorous PA and negative association with sitting), self-efficacy (i.e., positive association with vigorous PA), and resilience (i.e., positive association with walking). Although certain individual-level resilience resources were perceived as beneficial for PA and sedentary time, the moderating role of resilience resources was not supported by the findings. The direct and moderating effects between stress, PA, and resilience resources require further testing using longitudinal designs in which stressful periods occur naturally (e.g., exams for students) or are experimentally manipulated

An \u3cem\u3ein Vitro\u3c/em\u3e Assessment of Liposomal Topotecan Simulating Metronomic Chemotherapy in Combination with Radiation in Tumor-Endothelial Spheroids

Low dose metronomic chemotherapy (LDMC) refers to prolonged administration of low dose chemotherapy designed to minimize toxicity and target the tumor endothelium, causing tumor growth inhibition. Topotecan (TPT) when administered at its maximum tolerated dose (MTD) is often associated with systemic hematological toxicities. Liposomal encapsulation of TPT enhances efficacy by shielding it from systemic clearance, allowing greater uptake and extended tissue exposure in tumors. Extended release of TPT from liposomal formulations also has the potential to mimic metronomic therapies with fewer treatments. Here we investigate potential toxicities of equivalent doses of free and actively loaded liposomal TPT (LTPT) and compare them to a fractionated low dose regimen of free TPT in tumor-endothelial spheroids (TES) with/without radiation exposure for a prolonged period of 10 days. Using confocal microscopy, TPT fluorescence was monitored to determine the accumulation of drug within TES. These studies showed TES, being more reflective of the in vivo tumor microenvironment, were more sensitive to LTPT in comparison to free TPT with radiation. More importantly, the response of TES to low-dose metronomic TPT with radiation was comparable to similar treatment with LTPT. This TES study suggests nanoparticle formulations designed for extended release of drug can simulate LDMC in vivo

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines

Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937

Introduction—RTOG-0937 is a randomized phase-II trial evaluating 1-year OS with PCI or PCI plus consolidative radiation therapy (cRT) to intra-thoracic disease and extracranial metastases for ED-SCLC. Methods—Patients with 1–4 extracranial metastases were eligible after CR or PR to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included PR vs CR after chemotherapy and 1 vs 2–4 metastases; age \u3c 65 vs ≥ 65 was added after an observed imbalance. PCI was 25GY/10 fractions. cRT was 45GY/15 fractions. To detect an OS improvement from 30% to 45% with a 34% hazard reduction (HR=0·66) under a 0.1 type-1 error (1-sided) and 80% power, 154 patients were required. Results—Ninety-seven patients were randomized between March, 2010 and February, 2015. Eleven patients were ineligible (nine PCI, two PCI+cRT), leaving 42 randomized to PCI and 44 to PCI+cRT. At planned interim analysis the study crossed the futility boundary for OS and was closed prior to meeting accrual target. Median follow-up was 9 months. One-year OS was not different between the groups: 60.1% [95% CI: 41.2–74.7%] for PCI and 50.8% [95% CI:34.0–65.3%] for PCI+cRT (p=0.21). Three and 12-month rates of progression were 53.3% and 79.6% for PCI, and 14.5% and 75% for PCI+cRT. Time to progression favored PCI+cRT, HR=0.53 (95% CI: 0.32–0.87, p=0.01). One-patient in each arm had Grade-4 therapy related toxicity and one had Grade-5 therapy related pneumonitis with PCI+cRT. Conclusions—OS exceeded predictions for both arms. Consolidative RT delayed progression but did not improve 1-year OS

Spatial Pattern Enhances Ecosystem Functioning in an African Savanna

Termites indirectly enhance plant and animal productivity near their mounds, and the uniform spatial patterning of these mounds enhances the overall productivity of the entire landscape

Statistical Analysis of Choice Experiments and Surveys

Measures of households' past behavior, their expectations with respect to future events and contingencies, and their intentions with respect to future behavior are frequently collected using household surveys. These questions are conceptually difficult. Answering them requires elaborate cognitive and social processes, and often respondents report only their “best” guesses and/or estimates, using more or less sophisticated heuristics. A large body of literature in psychology and survey research shows that as a result, responses to such questions may be severely biased. In this paper, (1) we describe some of the problems that are typically encountered, (2) provide some empirical illustrations of these biases, and (3) develop a framework for conceptualizing survey response behavior and for integrating structural models of response behavior into the statistical analysis of the underlying economic behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47001/1/11002_2005_Article_5884.pd

Competition and Combative Advertising: An Historical Analysis

Fred K. Beard (PhD, University of Oklahoma) is a professor of advertising in the Gaylord College of Journalism and Mass Communication, University of Oklahoma. His research interests include comparative advertising, advertising humor, and advertising history. His work has appeared in the Journal of Advertising, the Journal of Advertising Research, the Journal of Business Ethics, the Journal of Business Research, Journalism History, the Journal of Historical Research in Marketing, the Journal of Macromarketing, and the Journal of Marketing Communications, among others.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570