Tachol1 QTL on mouse chromosome 1 is responsible for hypercholesterolemia and diet-induced obesity.

Hypercholesterolemia raises the risk for cardiovascular complications and overall health. Hypercholesterolemia is common, affecting 10% of the general population of the US, and heritable. Most individuals with hypercholesterolemia have a polygenic predisposition to the condition. Previously we identified a quantitative trait locus, Tachol1, linked to hypercholesterolemia on mouse chromosome 1 (Chr1) in a cross between C57BL/6J (B6) and TALLYHO/JngJ (TH) mice, a polygenic model for human obesity, type 2 diabetes and hyperlipidemia. Subsequently, using congenic mice that carry a TH-derived genomic segment of Chr1 on a B6 background, we demonstrated that the distal segment of Chr1, where Tachol1 maps, is necessary to cause hypercholesterolemia, as well as diet-induced obesity. In this study, we generated overlapping subcongenic lines to the distal segment of congenic region and characterized subcongenic mice carrying the smallest TH region of Tachol1, ~ 16.2 Mb in size (B6.TH-Chr1-16.2 Mb). Both male and female B6.TH-Chr1-16.2 Mb mice showed a significantly increased plasma total cholesterol levels compared to B6 on both chow and high fat (HF) diet. B6.TH-Chr1-16.2 Mb mice also had greater fat mass than B6 on HF diet, without increasing food intake. The gene and protein expression levels of absent in melanoma 2 (Aim2) gene were significantly upregulated in B6.TH-Chr1-16.2 Mb mice compared to B6. In summary, we confirmed the effect of Tachol1 on hypercholesterolemia and diet-induced obesity using subcongenic analysis.

Anti-factor Xa and activated partial thromboplastin time strategies for unfractionated heparin dosing after HeartMate 3 left ventricular assist device implantation.

BACKGROUND: No clear guidelines exist for perioperative anticoagulation management after durable left ventricular assist device insertion. In this study, we sought to compare outcomes between anti-factor Xa (FXa) and activated partial thromboplastin time (aPTT) in monitoring unfractionated heparin (UFH) dosing after HeartMate 3 (HM3) insertion. METHODS: This is a single-center retrospective review of patients who received UFH after HM3 insertion between 01/2020-12/2022. Post-operative UFH dose was titrated by aPTT goal 45-60 sec (n = 53) or FXa goal 0.1-0.2 U/mL (n = 59). Baseline differences between cohorts were balanced by inverse probability treatment weighting. RESULTS: At baseline, unadjusted FXa patients were more likely to be white (47.5% vs. 35.8%, p < 0.001), INTERMACS 1-2 (69.5% vs. 47.2%, p = 0.013), have history of coronary artery disease (66.1% vs. 43.4%, p = 0.026), and lower eGFR (54.1 vs. 63.7 mL/min/1.73 m2, p = 0.029) compared to the aPTT group. After adjusting for several bleeding/thrombosis risk factors, 97.5% of FXa and 91.0% of aPTT patients reached therapeutic levels with comparable UFH duration and maximum dose. Moreover, in-hospital mortality (2.5% vs. 3.1%, p = 0.842), major bleeding events (4.2% vs. 9.2%, p = 0.360), and thromboembolic events (21.8% vs. 10.1%, p = 0.151) remained without significant differences between FXa and aPTT cohorts. There was a high degree of variability in FXa (r2 = 0.20) and aPTT (r2 = 0.22) values for any given UFH dose. CONCLUSIONS: No differences in frequency of bleeding or thromboembolic events were observed in this study between FXa versus aPTT cohorts after HM3 implantation. More longitudinal studies are warranted to determine whether or not one assay is superior to the other.

Fluctuating pH for efficient photomixotrophic succinate production.

Cyanobacteria are attracting increasing attention as a photosynthetic chassis organism for diverse biochemical production, however, photoautotrophic production remains inefficient. Photomixotrophy, a method where sugar is used to supplement baseline autotrophic metabolism in photosynthetic hosts, is becoming increasingly popular for enhancing sustainable bioproduction with multiple input energy streams. In this study, the commercially relevant diacid, succinate, was produced photomixotrophically. Succinate is an important industrial chemical that can be used for the production of a wide array of products, from pharmaceuticals to biopolymers. In this system, the substrate, glucose, is transported by a proton symporter and the product, succinate, is hypothesized to be transported by another proton symporter, but in the opposite direction. Thus, low pH is required for the import of glucose and high pH is required for the export of succinate. Succinate production was initiated in a pH 7 medium containing bicarbonate. Glucose was efficiently imported at around neutral pH. Utilization of bicarbonate by CO2 fixation raised the pH of the medium. As succinate, a diacid, was produced, the pH of the medium dropped. By repeating this cycle with additional pH adjustment, those contradictory requirements for transport were overcome. pH affects a variety of biological factors and by cycling from high pH to neutral pH processes such as CO2 fixation rates and CO2 solubility can vary. In this study the engineered strains produced succinate during fluctuating pH conditions, achieving a titer of 5.0 g L-1 after 10 days under shake flask conditions. These results demonstrate the potential for photomixotrophic production as a viable option for the large-scale production of succinate.

Electrical-biological hybrid system for carbon efficient isobutanol production.

We have developed an electrical-biological hybrid system wherein an engineered microorganism consumes electrocatalytically produced formate from CO2 to supplement the bioproduction of isobutanol, a valuable fuel chemical. Biological CO2 sequestration is notoriously slow compared to electrochemical CO2 reduction, while electrochemical methods struggle to generate carbon-carbon bonds which readily form in biological systems. A hybrid system provides a promising method for combining the benefits of both biology and electrochemistry. Previously, Escherichia coli was engineered to assimilate formate and CO2 in central metabolism using the reductive glycine pathway. In this work, we have shown that chemical production in E. coli can benefit from single carbon substrates when equipped with the RGP. By installing the RGP and the isobutanol biosynthetic pathway into E. coli and by further genetic modifications, we have generated a strain of E. coli that can consume formate and produce isobutanol at a yield of >100% of theoretical maximum from glucose. Our results demonstrate that carbon produced from electrocatalytically reduced CO2 can bolster chemical production in E. coli. This study shows that E. coli can be engineered towards carbon efficient methods of chemical production.

Amorphous-Carbon-Coated 3D Solid Electrolyte for an Electro-Chemomechanically Stable Lithium Metal Anode in Solid-State Batteries.

The use of solid-state electrolyte may be necessary to enable safe, high-energy-density Li metal anodes for next-generation energy storage systems. However, the inhomogeneous local current densities during long-term cycling result in instability and detachment of the Li anode from the electrolyte, which greatly hinders practical application. In this study, we report a new approach to maintain a stable Li metal | electrolyte interface by depositing an amorphous carbon nanocoating on garnet-type solid-state electrolyte. The carbon nanocoating provides both electron and ion conducting capability, which helps to homogenize the lithium metal stripping and plating processes. After coating, we find the Li metal/garnet interface displays stable cycling at 3 mA/cm2 for more than 500 h, demonstrating the interface's outstanding electro-chemomechanical stability. This work suggests amorphous carbon coatings may be a promising strategy for achieving stable Li metal | electrolyte interfaces and reliable Li metal batteries.

Attention Deficit-Hyperactivity Disorder and Month of School Enrollment.

BACKGROUND: Younger children in a school grade cohort may be more likely to receive a diagnosis of attention deficit-hyperactivity disorder (ADHD) than their older peers because of age-based variation in behavior that may be attributed to ADHD rather than to the younger age of the children. Most U.S. states have arbitrary age cutoffs for entry into public school. Therefore, within the same grade, children with birthdays close to the cutoff date can differ in age by nearly 1 year. METHODS: We used data from 2007 through 2015 from a large insurance database to compare the rate of ADHD diagnosis among children born in August with that among children born in September in states with and states without the requirement that children be 5 years old by September 1 for enrollment in kindergarten. ADHD diagnosis was determined on the basis of diagnosis codes from the International Classification of Diseases, 9th Revision. We also used prescription records to compare ADHD treatment between children born in August and children born in September in states with and states without the cutoff date of September 1. RESULTS: The study population included 407,846 children in all U.S. states who were born in the period from 2007 through 2009 and were followed through December 2015. The rate of claims-based ADHD diagnosis among children in states with a September 1 cutoff was 85.1 per 10,000 children (309 cases among 36,319 children; 95% confidence interval [CI], 75.6 to 94.2) among those born in August and 63.6 per 10,000 children (225 cases among 35,353 children; 95% CI, 55.4 to 71.9) among those born in September, an absolute difference of 21.5 per 10,000 children (95% CI, 8.8 to 34.0); the corresponding difference in states without the September 1 cutoff was 8.9 per 10,000 children (95% CI, -14.9 to 20.8). The rate of ADHD treatment was 52.9 per 10,000 children (192 of 36,319 children; 95% CI, 45.4 to 60.3) among those born in August and 40.4 per 10,000 children (143 of 35,353 children; 95% CI, 33.8 to 47.1) among those born in September, an absolute difference of 12.5 per 10,000 children (95% CI, 2.43 to 22.4). These differences were not observed for other month-to-month comparisons, nor were they observed in states with non-September cutoff dates for starting kindergarten. In addition, in states with a September 1 cutoff, no significant differences between August-born and September-born children were observed in rates of asthma, diabetes, or obesity. CONCLUSIONS: Rates of diagnosis and treatment of ADHD are higher among children born in August than among children born in September in states with a September 1 cutoff for kindergarten entry. (Funded by the National Institutes of Health.).

Screening Sweetpotato Genotypes for Resistance to a North Carolina Isolate of Meloidogyne enterolobii.

Potential resistance to the guava root-knot nematode, Meloidogyne enterolobii, in 91 selected sweetpotato (Ipomoea batatas [L.] Lam.) genotypes was evaluated in six greenhouse experiments. Ten thousand eggs of M. enterolobii were inoculated on each sweetpotato genotype grown in a 3:1 sand to soil mixture. Sixty days after inoculation, the percentage of total roots with nematode-induced galls was determined, and nematode eggs were extracted from roots. Significant differences (P < 0.001) between sweetpotato genotypes were found in all six tests for gall rating, total eggs, and eggs per gram of root. Resistant sweetpotato genotypes were calculated as final eggs per root system divided by the initial inoculum, where Pf/Pi < 1 (reproduction factor; final egg count divided by initial inoculum of 10,000 eggs), and statistical mean separations were confirmed by Fisher's least significant difference t test. Our results indicated that 19 out of 91 tested sweetpotato genotypes were resistant to M. enterolobii. Some of the susceptible genotypes included 'Covington,' 'Beauregard,' 'NCDM04-001', and 'Hernandez.' Some of the resistant sweetpotato genotypes included 'Tanzania,' 'Murasaki-29,' 'Bwanjule,' 'Dimbuka-Bukulula,' 'Jewel,' and 'Centennial.' Most of the 19 resistant sweetpotato genotypes supported almost no M. enterolobii reproduction, with <20 eggs/g root of M. enterolobii. A number of segregants from a 'Tanzania' × 'Beauregard' cross demonstrated strong resistance to M. enterolobii observed in the 'Tanzania' parent. In collaboration with North Carolina State University sweetpotato breeding program, several genotypes evaluated in these tests are being used to incorporate the observed resistance to M. enterolobii into commercial sweetpotato cultivars.

Virtual estimation of effective dose in neutron fields.

The PODIUM project aims to provide real-time assessments of occupationally exposed workers by tracking their motion and combining this with a simulation of the radiation field. The present work describes the approach that would be taken in mixed neutron-gamma fields, and details the methods for generating and applying an effective dose rate map; the required fluence to effective dose conversion coefficients at intercardinal angles are also presented. A proof-of-concept of the approach is demonstrated using a simple simulated workplace field within a calibration laboratory, with corroborative comparisons made against survey instrument measurements generally confirming good agreement. Simulated tracking of an individual within the facility was performed, recording a 1.25µSv total effective dose and accounting for dose rates as low as 0.5 nSv h-1, which is much lower than anything that could be accurately measured by physical neutron dosemeters in such a field.

Quality assurance for the use of computational methods in dosimetry: activities of EURADOS Working Group 6 'Computational Dosimetry'.

Working Group (WG) 6 'Computational Dosimetry' of the European Radiation Dosimetry Group promotes good practice in the application of computational methods for radiation dosimetry in radiation protection and the medical use of ionising radiation. Its cross-sectional activities within the association cover a large range of current topics in radiation dosimetry, including more fundamental studies of radiation effects in complex systems. In addition, WG 6 also performs scientific research and development as well as knowledge transfer activities, such as training courses. Monte Carlo techniques, including the use of anthropomorphic and other numerical phantoms based on voxelised geometrical models, play a strong part in the activities pursued in WG 6. However, other aspects and techniques, such as neutron spectra unfolding, have an important role as well. A number of intercomparison exercises have been carried out in the past to provide information on the accuracy with which computational methods are applied and whether best practice is being followed. Within the exercises that are still ongoing, the focus has changed towards assessing the uncertainty that can be achieved with these computational methods. Furthermore, the future strategy of WG 6 also includes an extension of the scope toward experimental benchmark activities and evaluation of cross-sections and algorithms, with the vision of establishing a gold standard for Monte Carlo methods used in medical and radiobiological applications.

Medicare Reimbursement to Physicians Decreased for Common Emergency Medicine Services From 2000 to 2020.

STUDY OBJECTIVE: The change in reimbursement rates for emergency physician services has yet to be quantified. We attempted to fill this knowledge gap by evaluating the monetary trends in Medicare reimbursement rates over the last 20 years for the most common emergency medicine services. METHODS: We obtained commonly used Current Procedural Terminology (CPT) codes in emergency medicine from the American College of Emergency Physicians website. We queried the Physician Fee Schedule Look-Up Tool from the Centers for Medicare & Medicaid Services for each of the included CPT codes, and we extracted reimbursement data. We adjusted all monetary data for inflation to 2020 US dollars by using changes to the United States consumer price index. Both the average annual and the total percentage change in reimbursement were calculated on the basis of these adjusted trends for all included services. RESULTS: Reimbursement by Medicare for the services decreased by an average of 29.13% from 2000 to 2020 after adjusting for inflation. There was a stable decline in adjusted reimbursement rates throughout the study period, with an average decrease of 1.61% each year. The largest decrease was seen for laceration repairs up to 7.5 cm, with reimbursement rates for all 4 relevant CPT codes decreasing by more than 60%. CONCLUSION: When adjusted for inflation, Medicare reimbursement declined by an average of 29% over the last 20 years for the 20 most common emergency medicine services. Knowledge of these trends is essential to address current controversies in emergency medicine billing adequately and advocate for sustainable payment system reform.

Three-Dimensional, Solid-State Mixed Electron-Ion Conductive Framework for Lithium Metal Anode.

Solid-state electrolytes (SSEs) have been widely considered as enabling materials for the practical application of lithium metal anodes. However, many problems inhibit the widespread application of solid state batteries, including the growth of lithium dendrites, high interfacial resistance, and the inability to operate at high current density. In this study, we report a three-dimensional (3D) mixed electron/ion conducting framework (3D-MCF) based on a porous-dense-porous trilayer garnet electrolyte structure created via tape casting to facilitate the use of a 3D solid state lithium metal anode. The 3D-MCF was achieved by a conformal coating of carbon nanotubes (CNTs) on the porous garnet structure, creating a composite mixed electron/ion conductor that acts as a 3D host for the lithium metal. The lithium metal was introduced into the 3D-MCF via slow electrochemical deposition, forming a 3D lithium metal anode. The slow lithiation leads to improved contact between the lithium metal anode and garnet electrolyte, resulting in a low resistance of 25 Ω cm2. Additionally, due to the continuous CNT coating and its seamless contact with the garnet we observed highly uniform lithium deposition behavior in the porous garnet structure. With the same local current density, the high surface area of the porous garnet framework leads to a higher overall areal current density for stable lithium deposition. An elevated current density of 1 mA/cm2 based on the geometric area of the cell was demonstrated for continuous lithium cycling in symmetric lithium cells. For battery operation of the trilayer structure, the lithium can be cycled between the 3D-MCF on one side and the cathode infused into the porous structure on the opposite side. The 3D-MCF created by the porous garnet structure and conformal CNT coating provides a promising direction toward new designs in solid-state lithium metal batteries.

Moving bed biofilm reactor technology in municipal wastewater treatment: A review.

The review encompasses the development of municipal wastewater treatment process using MBBR from early stages, established application, and recent advancements. An overview of main drivers leading to the MBBR technology development over its early stage is discussed. Biocarriers types and features together with biofilm development and role of extracellular polymeric substances (EPS) are presented, ultimately, addressing the challenge in decreasing startup time required for full operation. Furthermore, the review investigates the state of the art of MBBR technology for nutrient removal (i.e., COD and BOD, nitrogen and phosphorus) through process functionality and configuration of established (e.g., IFAS) and under development (e.g. PN/A) applications. Reactor operational characteristics such as filling fractions, mixing properties, dissolved oxygen requirements, and loading rates are presented and related to full scale examples. Current literature discussing the most recent studies on MBBR capability in reduction and removal of chemicals of emerging concern (CEC) released is presented. Ultimately, high rate carbon and nitrogen removal through A/B stage process are examined in its main operational parameters and its application towards energy neutrality suggesting novel MBBR application to further reduce energy requirements and plant footprint.

The effects of revised operational dose quantities on the response characteristics of a beta/gamma personal dosemeter.

The International Commission on Radiation Units and Measurements is considering revising the definitions of the operational dose quantities used for personal monitoring. This paper investigates the impacts of the proposed changes on the Public Health England two-element ß/γ personal thermoluminescence dosemeter (TLD), in terms of its energy and angle dependences of responses for both skin and whole-body dose assessments. In general, the photon response of the skin element would be unaffected by the proposal, though technical issues may arise during calibration. For body photon doses, the current TLD design still produces acceptable response characteristics in some circumstances, but in general it will need to be redesigned to better match the requirements of the new operational quantity; to that end, a simple adaption is demonstrated that might provide a partial solution. For electron/beta exposures, matching the combined responses of both the body and skin elements to the dose quantities may be more challenging. The performance criteria against which dosemeters are judged may also need to be revised to reflect the proposed change.

EURADOS education and training activities.

This paper provides a summary of the Education and Training (E&T) activities that have been developed and organised by the European Radiation Dosimetry Group (EURADOS) in recent years and in the case of Training Courses over the last decade. These E&T actions include short duration Training Courses on well-established topics organised within the activity of EURADOS Working Groups (WGs), or one-day events integrated in the EURADOS Annual Meeting (workshops, winter schools, the intercomparison participants' sessions and the learning network, among others). Moreover, EURADOS has recently established a Young Scientist Grant and a Young Scientist Award. The Grant supports young scientists by encouraging them to perform research projects at other laboratories of the EURADOS network. The Award is given in recognition of excellent work developed within the WGs' work programme. Additionally, EURADOS supports the dissemination of knowledge in radiation dosimetry by promoting and endorsing conferences such as the individual monitoring (IM) series, the neutron and ion dosimetry symposia (NEUDOS) and contributions to E&T sessions at specific events.

Sealed osteons in animals and humans: low prevalence and lack of relationship with age.

Sealed osteons are unusual variants of secondary osteons that have received little attention, especially in non-human bones. Sealed osteons are characterized by central canals that are plugged with bone tissue. As with other variants of secondary osteons (e.g. drifting, dumbbell, multi-canal), understanding how and why sealed osteons form can shed light on the mechanisms that regulate normal bone remodeling and how this process can be perturbed with aging and some diseases. In a recent microscopic evaluation of human tibiae obtained after traumatic amputations, 4-5% of the osteons were sealed. It is suggested that this high prevalence reflects occasional localized microscopic ischemia from normal osteonal remodeling; hence sealed osteons are implicated in human skeletal fragility. Therefore, osteon prevalence would be expected to correlate with the bone remodeling seen with aging; for example, showing positive relationships between sealed osteons and the population density of typical secondary osteons (OPD). We evaluated the prevalence of partially sealed (80-99% sealed) and fully sealed osteons with respect to age and variations in OPD in 10 adult human femora (34-71 years) and in various non-human appendicular bones of mature animals that were not of advanced age, including deer calcanei, equine radii and equine third metacarpals. An additional sample of 10 bilateral human femora with unilateral non-cemented total hip replacements (F,+HR) and non-implanted contralateral femora (F,-HR) were evaluated (10 patients; 52-94 years). In non-human bones, sealed + partially sealed osteons were rare (~0.1%) even when having relatively high OPD. When considering sealed + partially sealed osteons in femora from patients without any HR, results showed that 1.6% of the osteons were sealed or partially sealed, which was much lower than anticipated, but this is 10- to 20-fold more than in any of the non-human bones. Additionally, in all bones, sealed + partially sealed osteons were significantly smaller than typical secondary osteons (mean diameters: 125 vs. 272 µm; P < 0.005). In the patients with HR, the percentage of sealed + partially sealed osteons: (i) did not correlate with age, (ii) showed no significant difference between F,-HR and F,+HR (1.9 vs. 2.1%; P = 0.2), and (iii) was positively correlated with OPD (r = 0.67, P = 0.001), which differs from the very weak or lack of correlations in the non-human bones and the other human femur sample. The lack of an age-related relationship, in addition to the very low prevalence of sealed + partially sealed osteons are inconsistent with the idea that they contribute to reduced bone quality seen in aging humans. The small size of sealed and partially sealed osteons, regardless of species affiliation, suggests that they represent closing cones at the termini of some osteons. Available evidence suggests that osteons of primates might have a greater capacity for branching that is associated with closing cones, which might explain the 10-20 times higher prevalence of sealed + partially sealed osteons in the human bones examined in this study.

The effects of a revised operational dose quantity on the response characteristics of neutron survey instruments.

The ICRU is considering revising the definition of ambient dose equivalent. This paper investigates the impacts of the proposed change on four designs of neutron survey instrument, the GNU, HSREM, LB6411 and Studsvik 2202D, in terms of their respective energy dependences of response and their performances in realistic workplace fields. In some circumstances the current designs of instrument still produce acceptable characteristics, but in general they may need to be re-optimized to better match the requirements of the new operational quantity; to that end, a simple retrofit solution for the GNU is demonstrated. The performance criteria against which instruments are judged may also need to be revised to reflect the proposed change.

Transcatheter Mitral Valve-in-Ring Implantation.

Failed surgical mitral valve repair using an annuloplasty ring has traditionally been treated with surgical valve replacement or repair1. For patients at high risk for repeat open heart surgery, placement of a trans-catheter aortic valve (i.e., TAVI valve) within the mitral ring (i.e., Mitral-Valve-in-Ring, MViR) has emerged as a novel alternative treatment strategy2-5 . We describe our experience of a failed mitral valve repair that was successfully treated with a TAVI valve delivered via the trans-septal approach, and summarise the data relating to this emerging treatment strategy.

Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network.

In embryonic stem cells (ESCs), gene regulatory networks (GRNs) coordinate gene expression to maintain ESC identity; however, the complete repertoire of factors regulating the ESC state is not fully understood. Our previous temporal microarray analysis of ESC commitment identified the E3 ubiquitin ligase protein Makorin-1 (MKRN1) as a potential novel component of the ESC GRN. Here, using multilayered systems-level analyses, we compiled a MKRN1-centered interactome in undifferentiated ESCs at the proteomic and ribonomic level. Proteomic analyses in undifferentiated ESCs revealed that MKRN1 associates with RNA-binding proteins, and ensuing RIP-chip analysis determined that MKRN1 associates with mRNAs encoding functionally related proteins including proteins that function during cellular stress. Subsequent biological validation identified MKRN1 as a novel stress granule-resident protein, although MKRN1 is not required for stress granule formation, or survival of unstressed ESCs. Thus, our unbiased systems-level analyses support a role for the E3 ligase MKRN1 as a ribonucleoprotein within the ESC GRN.

A Rare Cause of Testicular Pain: Thrombosis of the Pampiniform Plexus.

Testicular pain is a common presentation in the emergency department. The cause includes a wide array of differentials. This report highlights a case of thrombosis of the pampiniform plexus as a rare cause of testicular pain. Doppler ultrasound should be the first line investigation. Symptomatic relief with anti-inflammatory medication should be sufficient for management.

Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic PEEP in COPD?

INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume-time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied 19 patients (n=8 mild-moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV1 in the whole cohort (r=-0.71, p<0.001) and patients alone (r=-0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=-0.55, p=0.0015) and patients (r=-0.71, p<0.001) and peak exercise tidal volume (r=-0.58, p=0.0062 and r=-0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=-0.65, p<0.001) and patients considered alone (r=-0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=-0.69, p<0.001) and patients (r=-0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity.