Hybrid Gear Preliminary Results-Application of Composites to Dynamic Mechanical Components

Composite spur gears were fabricated and then tested at NASA Glenn Research Center. The composite material served as the web of the gear between the gear teeth and a metallic hub for mounting to the torque-applying shaft. The composite web was bonded only to the inner and outer hexagonal features that were machined from an initially all-metallic aerospace quality spur gear. The Hybrid Gear was tested against an all-steel gear and against a mating Hybrid Gear. As a result of the composite to metal fabrication process used, the concentricity of the gears were reduced from their initial high-precision value. Regardless of the concentricity error, the hybrid gears operated successfully for over 300 million cycles at 10000 rpm and 490 in.*lbs torque. Although the design was not optimized for weight, the composite gears were found to be 20% lighter than the all-steel gears. Free vibration modes and vibration/noise tests were also conduct to compare the vibration and damping characteristic of the Hybrid Gear to all-steel gears. The initial results indicate that this type of hybrid design may have a dramatic effect on drive system weight without sacrificing strength

A Novel Waveform to Extract Exercise Gas Exchange Response Dynamics: The Chirp Waveform

Characterizing exercise gas exchange response dynamics reveals important information about physiological control processes and cardiopulmonary dysfunction. However, current methods for extracting exercise response dynamics typically use multiple step-wise transitions, limiting applicability of this technique. PURPOSE: We designed a new protocol (chirp waveform) to extract exercise gas exchange response dynamics in a single visit. We tested the hypothesis that gas exchange response dynamics extracted from chirp forcing would be similar to those extracted from step-wise transitions. METHODS: Thirty-one participants (14 young healthy, 7 older healthy, and 10 patients with chronic obstructive pulmonary disease) visited the laboratory on three occasions. On visit 1, participants performed a ramp incremental test to determine the gas exchange threshold (GET). On visits 2-3, participants performed either a chirp or step-wise protocol in a randomized order. Chirp forcing consisted of sinusoidal fluctuations in work rate with constant amplitude and progressive shortening of sine periods. Square protocol consisted of 3 square-wave transitions each of 6 min duration. Work rate amplitude (from 20 W to ~95% of the individual’s GET) and exercise duration (30 min) were the same in both protocols. The input-output relationship was characterized using a first-order linear transfer function containing a system gain (K) and time constant (τ) [G(s)= K/(τ×s+1)]. Parameter identification was performed in Matlab using the Matlab System Identification toolbox. Agreement between measures was established using Bland-Altman analysis and Rothery’s Concordance Coefficient (RCC). RESULTS: No systematic bias (mean difference of chirp minus square-wave; Δmean) and good reliability was found for V̇O2 K [Δmean: 0.25(1.03) mL/min/W, p=0.179; RCC: 0.773, p=0.004], V̇O2 τ [Δmean: 0.30(7.08) s, p=0.815; RCC: 0.837, p2 K [Δmean: -0.19(1.57) mL/min/W, p=0.512; RCC: 0.827, pp=0.009] and good reliability (RCC: 0.794, p2 τ. CONCLUSION: The chirp waveform allows extraction of gas exchange response dynamics similar to those obtained from standard methods, thus overcoming the need for multiple tests

Is a Two-Day Cardiopulmonary Exercise Test a Valid Tool for The Diagnosis of Post-Exertional Malaise in Long COVID?

A two-day cardiopulmonary exercise testing (CPET) protocol (maximal ramp-incremental cycle test repeated 24hr apart) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients has suggested that day-2 performance is decreased relative to day-1. This difference has been attributed to post-exertional malaise (PEM), suggesting the two-day CPET as a protocol to investigate PEM in Long COVID (LC) patients. PURPOSE: We aimed to investigate any effects of PEM on exercise performance and cardiorespiratory and perceptual responses to a two-day CPET in LC patients to determine whether the day-1 CPET would impair performance, cardiorespiratory responses or perceptions of exercise at day-2. METHODS: Fifteen LC patients with one or more symptoms persisting for more than three months after their initial infection [n=7 females; n=1 hospitalized; mean(SD); age 53(11) yrs; body mass index 32.2(8.5) kg/m2; time between COVID-19 onset and CPET 13(7) months; forced expiratory volume in 1 second 89(15) %pred; forced vital capacity 92(14) %pred; diffusing capacity of the lungs for carbon monoxide 92(15) %pred; total lung capacity 86(12) %pred] were studied. Prior to any exercise testing, PEM was assessed relative to the past six months using the modified DePaul Symptom Questionnaire (mDSQ) (0-4 symptoms frequency and severity scores). Each performed a two-day CPET protocol; ramp was 10-20 W/min, with the same ramp rate used for the day-1 and day-2 CPET. Peak oxygen uptake, peak work rate, and gas exchange threshold were measured using standard techniques. Ratings of perceived dyspnea and leg effort during cycling were recorded at peak exercise using the modified Borg’s Scale (0-10). One-sample t-tests were used to assess significance of test-retest mean difference. RESULTS: The mDSQ indicated the presence of PEM symptoms in 80% of participants. However, no significant differences between day-1 and day-2 CPET were found in any of the variables assessed. CONCLUSION: The absence of any difference in cardiorespiratory and perceptual responses in 2-day CPET testing, despite patient reported presence of PEM symptoms, suggests that the two-day CPET protocol may not be a valid tool for the diagnosis of PEM in LC patients

The purpose of mess in action research: building rigour though a messy turn

Mess and rigour might appear to be strange bedfellows. This paper argues that the purpose of mess is to facilitate a turn towards new constructions of knowing that lead to transformation in practice (an action turn). Engaging in action research - research that can disturb both individual and communally held notions of knowledge for practice - will be messy. Investigations into the 'messy area', the interface between the known and the nearly known, between knowledge in use and tacit knowledge as yet to be useful, reveal the 'messy area' as a vital element for seeing, disrupting, analysing, learning, knowing and changing. It is the place where long-held views shaped by professional knowledge, practical judgement, experience and intuition are seen through other lenses. It is here that reframing takes place and new knowing, which has both theoretical and practical significance, arises: a 'messy turn' takes place

An Empirical Approach to Defining Loss to Follow-up Among Patients Enrolled in Antiretroviral Treatment Programs

In many programs providing antiretroviral therapy (ART), clinicians report substantial patient attrition; however, there are no consensus criteria for defining patient loss to follow-up (LTFU). Data on a multisite human immunodeficiency virus (HIV) treatment cohort in Lusaka, Zambia, were used to determine an empirical “days-late” definition of LTFU among patients on ART. Cohort members were classified as either “in care” or LTFU as of December 31, 2007, according to a range of days-late intervals. The authors then looked forward in the database to determine which patients actually returned to care at any point over the following year. The interval that best minimized LTFU misclassification was described as “best-performing.” Overall, 33,704 HIV-infected adults on ART were included. Nearly one-third (n = 10,196) were at least 1 day late for an appointment. The best-performing LTFU definition was 56 days after a missed visit, which had a sensitivity of 84.1% (95% confidence interval (CI): 83.2, 85.0), specificity of 97.5% (95% CI: 97.3, 97.7), and misclassification of 5.1% (95% CI: 4.8, 5.3). The 60-day threshold performed similarly well, with only a marginal difference (<0.1%) in misclassification. This analysis suggests that ≥60 days since the last appointment is a reasonable definition of LTFU. Standardization to empirically derived definitions of LTFU will permit more reliable comparisons within and across programs

A new bronchodilator response grading strategy ıdentifies distinct patient populations

Rationale: A positive bronchodilator response (BDR) according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines require both 200 ml and 12% increase in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after bronchodilator inhalation. This dual criterion is insensitive in those with high or low FEV1. Objectives: To establish BDR criteria with volume or percentage FEV1 change. Methods: The largest FEV1 and FVC were identified fromthree pre- and three post-bronchodilator maneuvers in COPDGene (Genetic Epidemiology of COPD) participants. A total of 7,741 individuals with coefficient of variation less than 15% for both FEV1 and FVC formed bronchodilator categories of FEV1 response: negative (0.00% to 0.00 L to 9.00% to 16.00% to 0.16 L to 26.00% or >0.26 L). These response size categories are based on empirical limits considering average FEV1 increase of approximately 160 ml and the clinically important difference for FEV1. To compare flow and volume response characteristics, BDR-FEV1 category assignments were applied for the BDR-FVC response. Results: Twenty percent met mild and 31% met moderate or marked BDR-FEV1 criteria, whereas 12% met mild and 33% met moderate or marked BDR-FVC criteria. In contrast, only 20.6% met ATS/ERS positive criteria. Compared with the negative BDR-FEV1 category, the minimal, mild, moderate, and marked BDR-FEV1 categories were associated with greater 6-minute-walk distance and lower St. George's Respiratory Questionnaire and modified Medical Research Council dyspnea scale scores. Compared with negative BDR, moderate and marked BDR-FEV1 categories were associated with fewer exacerbations, and minimal BDR was associated with lower computed tomography airway wall thickness. Compared with the negative category, all BDR-FVC categories were associated with increasing emphysema percentage and gas trapping percentage. Moderate and marked BDR-FVC categories were associated with higher St. George's Respiratory Questionnaire scores but fewer exacerbations and lower dyspnea scores. Conclusions: BDR grading by FEV1 volume or percentage response identified subjects otherwise missed by ATS/ERS criteria. BDR grades were associated with functional exercise performance, quality of life, exacerbation frequency, dyspnea, and radiological airway measures. BDR grades in FEV1 and FVC indicate different clinical and radiological characteristics.United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI)National Center for Advancing Translational Sciences through UCLA CTSI Gran

Hot Streaks in Artistic, Cultural, and Scientific Careers

The hot streak, loosely defined as winning begets more winnings, highlights a specific period during which an individual's performance is substantially higher than her typical performance. While widely debated in sports, gambling, and financial markets over the past several decades, little is known if hot streaks apply to individual careers. Here, building on rich literature on lifecycle of creativity, we collected large-scale career histories of individual artists, movie directors and scientists, tracing the artworks, movies, and scientific publications they produced. We find that, across all three domains, hit works within a career show a high degree of temporal regularity, each career being characterized by bursts of high-impact works occurring in sequence. We demonstrate that these observations can be explained by a simple hot-streak model we developed, allowing us to probe quantitatively the hot streak phenomenon governing individual careers, which we find to be remarkably universal across diverse domains we analyzed: The hot streaks are ubiquitous yet unique across different careers. While the vast majority of individuals have at least one hot streak, hot streaks are most likely to occur only once. The hot streak emerges randomly within an individual's sequence of works, is temporally localized, and is unassociated with any detectable change in productivity. We show that, since works produced during hot streaks garner significantly more impact, the uncovered hot streaks fundamentally drives the collective impact of an individual, ignoring which leads us to systematically over- or under-estimate the future impact of a career. These results not only deepen our quantitative understanding of patterns governing individual ingenuity and success, they may also have implications for decisions and policies involving predicting and nurturing individuals with lasting impact

Identifying a Heart Rate Recovery Criterion After a 6-Minute Walk Test in COPD

Background: Slow heart rate recovery (HRR) after exercise is associated with autonomic dysfunction and increased mortality. What HRR criterion at 1-minute after a 6-minute walk test (6MWT) best defines pulmonary impairment?. Study Design and Methods: A total of 5008 phase 2 COPDGene (NCT00608764) participants with smoking history were included. A total of 2127 had COPD and, of these, 385 were followed-up 5-years later. Lung surgery, transplant, bronchiectasis, atrial fibrillation, heart failure and pacemakers were exclusionary. HR was measured from pulse oximetry at end-walk and after 1-min seated recovery. A receiver operator characteristic (ROC) identified optimal HRR cut-off. Generalized linear regression determined HRR association with spirometry, chest CT, symptoms and exacerbations. Results: HRR after 6MWT (bt/min) was categorized in quintiles: ≤ 5 (23.0% of participants), 6– 10 (20.7%), 11– 15 (18.9%), 16– 22 (18.5%) and ≥ 23 (18.9%). Compared to HRR≤ 5, HRR≥ 11 was associated with (p\u3c 0.001): lower pre-walk HR and 1-min post HR; greater end-walk HR; greater 6MWD; greater FEV1%pred; lower airway wall area and wall thickness. HRR was positively associated with FEV1%pred and negatively associated with airway wall thickness. An optimal HRR ≤ 10 bt/min yielded an area under the ROC curve of 0.62 (95% CI 0.58– 0.66) for identifying FEV1\u3c 30%pred. HRR≥ 11 bt/min was the lowest HRR associated with consistently less impairment in 6MWT, spirometry and CT variables. In COPD, HRR≤ 10 bt/min was associated with (p\u3c 0.001): ≥ 2 exacerbations in the previous year (OR=1.76[1.33– 2.34]); CAT≥ 10 (OR=1.42[1.18– 1.71]); mMRC≥ 2 (OR=1.42[1.19– 1.69]); GOLD 4 (OR=1.98[1.44– 2.73]) and GOLD D (OR=1.51[1.18– 1.95]). HRR≤ 10 bt/min was predicted COPD exacerbations at 5-year follow-up (RR=1.83[1.07– 3.12], P=0.027). Conclusion: HRR≤ 10 bt/min after 6MWT in COPD is associated with more severe expiratory flow limitation, airway wall thickening, worse dyspnoea and quality of life, and future exacerbations, suggesting that an abnormal HRR≤ 10 bt/min after a 6MWT may be used in a comprehensive assessment in COPD for risk of severity, symptoms and future exacerbations

A Preclinical Ultrasound Method for the Assessment of Vascular Disease Progression in Murine Models

INTRODUCTION: The efficacy of preclinical ultrasound at providing a quantitative assessment of mouse models of vascular disease is relatively unknown. In this study, preclinical ultrasound was used in combination with a semi-automatic image processing method to track arterial distension alterations in mouse models of abdominal aortic aneurysm and atherosclerosis. METHODS: Longitudinal B-mode ultrasound images of the abdominal aorta were acquired using a preclinical ultrasound scanner. Arterial distension was assessed using a semi-automatic image processing algorithm to track vessel wall motion over the cardiac cycle. A standard, manual analysis method was applied for comparison. RESULTS: Mean arterial distension was significantly lower in abdominal aortic aneurysm mice between day 0 and day 7 post-onset of disease (p < 0.01) and between day 0 and day 14 (p < 0.001), while no difference was observed in sham control mice. Manual analysis detected a significant decrease (p < 0.05) between day 0 and day 14 only. Atherosclerotic mice showed alterations in arterial distension relating to genetic modification and diet. Arterial distension was significantly lower (p < 0.05) in Ldlr−/−(++/−−) mice fed high-fat western diet when compared with both wild type (++/++) mice and Ldlr−/−(++/−−) mice fed chow diet. The manual method did not detect a significant difference between these groups. CONCLUSIONS: Arterial distension can be used as an early marker for the detection of arterial disease in murine models. The semi-automatic analysis method provided increased sensitivity to differences between experimental groups when compared to the manual analysis method

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease