The relationships between the campus built environment and walking activity.

Despite the gradual development of students' sedentary habits and associated health problems, only a few studies have extensively and systematically measured campus built environments (CBE) and their impact on street walking activity. This study explores the association between CBEs and pedestrian volume (PV). Comprehensive questionnaires, field audits, and GIS were used to measure the CBE variables and PV of 892 street segments on eight Chinese campuses in Tianjin. We used negative binomial regression models without spatial autocorrelations to investigate the relationship between the CBEs and PV. The findings indicated that campus Walk Score, facility and residential land ratio, campus design qualities, sidewalk conditions, street amenities, and other streetscape features were positively associated with PV. This study presents implications for campus research and planning practices in designing a pedestrian-friendly, sustainable, and healthy campus.

Sex differences in treatments and outcomes of patients with cardiogenic shock: a systematic review and epidemiological meta-analysis.

BACKGROUND: Women are at higher risk of mortality from many acute cardiovascular conditions, but studies have demonstrated differing findings regarding the mortality of cardiogenic shock in women and men. To examine differences in 30-day mortality and mechanical circulatory support use by sex in patients with cardiogenic shock. MAIN BODY: Cochrane Central, PubMed, MEDLINE and EMBASE were searched in April 2024. Studies were included if they were randomised controlled trials or observational studies, included adult patients with cardiogenic shock, and reported at least one of the following outcomes by sex: raw mortality, adjusted mortality (odds ratio) or use of mechanical circulatory support. Out of 4448 studies identified, 81 met inclusion criteria, pooling a total of 656,754 women and 1,018,036 men. In the unadjusted analysis for female sex and combined in-hospital and 30-day mortality, women had higher odds of mortality (Odds Ratio (OR) 1.35, 95% confidence interval (CI) 1.26-1.44, p < 0.001). Pooled unadjusted mortality was 35.9% in men and 40.8% in women (p < 0.001). When only studies reporting adjusted ORs were included, combined in-hospital/30-day mortality remained higher in women (OR 1.10, 95% CI 1.06-1.15, p < 0.001). These effects remained consistent across subgroups of acute myocardial infarction- and heart failure- related cardiogenic shock. Overall, women were less likely to receive mechanical support than men (OR = 0.67, 95% CI 0.57-0.79, p < 0.001); specifically, they were less likely to be treated with intra-aortic balloon pump (OR = 0.79, 95% CI 0.71-0.89, p < 0.001) or extracorporeal membrane oxygenation (OR = 0.84, 95% 0.71-0.99, p = 0.045). No significant difference was seen with use of percutaneous ventricular assist devices (OR = 0.82, 95% CI 0.51-1.33, p = 0.42). CONCLUSION: Even when adjusted for confounders, mortality for cardiogenic shock in women is approximately 10% higher than men. This effect is seen in both acute myocardial infarction and heart failure cardiogenic shock. Women with cardiogenic shock are less likely to be treated with mechanical circulatory support than men. Clinicians should make immediate efforts to ensure the prompt diagnosis and aggressive treatment of cardiogenic shock in women.

Bootstrapping a powerful mixed portmanteau test for time series.

A new portmanteau test statistic is proposed for detecting nonlinearity in time series data. The new portmanteau statistic is calculated from the log of the determinant of a matrix comprised of the autocorrelations and cross-correlations of the residuals and squared residuals of a fitted time series. The asymptotic distribution of the proposed test statistic is derived as a linear combination of chi-square distributed random variables and can be approximated by a gamma distribution. A bootstrapping approach is shown to be robust when distributional assumptions are relaxed. The efficacy of the statistic is studied against linear and nonlinear dependency structures of some stationary time series models. It is shown that the new test can provide higher power than other tests in many situations. We demonstrate the advantages of the proposed test by investigating linear and nonlinear effects in an economic series and two environmental time series.

Protocol to visualize ion channel trafficking in acutely isolated rodent neurons using live-cell immunocytochemistry.

Here, we present a protocol for live-cell immunocytochemistry to demonstrate reversible translocation of ion channels to the neuronal cell surface. We describe steps for cell preparation and isolation, experimental treatment, antibody binding prior to fixation, specific pipetting techniques, troubleshooting, and expected outcomes of correct use of the protocol. This protocol will be useful to study regulated translocation of ion channels and other membrane proteins. For complete details on the use and execution of this protocol, please refer to Haan et al.1.

Specialist hybrid models with asymmetric training for malaria prevalence prediction.

Malaria is a common and serious disease that primarily affects developing countries and its spread is influenced by a variety of environmental and human behavioral factors; therefore, accurate prevalence prediction has been identified as a critical component of the Global Technical Strategy for Malaria from 2016 to 2030. While traditional differential equation models can perform basic forecasting, supervised machine learning algorithms provide more accurate predictions, as demonstrated by a recent study using an elastic net model (REMPS). Nevertheless, current short-term prediction systems do not achieve the required accuracy levels for routine clinical practice. To improve in this direction, stacked hybrid models have been proposed, in which the outputs of several machine learning models are aggregated by using a meta-learner predictive model. In this paper, we propose an alternative specialist hybrid approach that combines a linear predictive model that specializes in the linear component of the malaria prevalence signal and a recurrent neural network predictive model that specializes in the non-linear residuals of the linear prediction, trained with a novel asymmetric loss. Our findings show that the specialist hybrid approach outperforms the current state-of-the-art stacked models on an open-source dataset containing 22 years of malaria prevalence data from the city of Ibadan in southwest Nigeria. The specialist hybrid approach is a promising alternative to current prediction methods, as well as a tool to improve decision-making and resource allocation for malaria control in high-risk countries.

A comparative study of model-centric and data-centric approaches in the development of cardiovascular disease risk prediction models in the UK Biobank.

Aims: A diverse set of factors influence cardiovascular diseases (CVDs), but a systematic investigation of the interplay between these determinants and the contribution of each to CVD incidence prediction is largely missing from the literature. In this study, we leverage one of the most comprehensive biobanks worldwide, the UK Biobank, to investigate the contribution of different risk factor categories to more accurate incidence predictions in the overall population, by sex, different age groups, and ethnicity. Methods and results: The investigated categories include the history of medical events, behavioural factors, socioeconomic factors, environmental factors, and measurements. We included data from a cohort of 405 257 participants aged 37-73 years and trained various machine learning and deep learning models on different subsets of risk factors to predict CVD incidence. Each of the models was trained on the complete set of predictors and subsets where each category was excluded. The results were benchmarked against QRISK3. The findings highlight that (i) leveraging a more comprehensive medical history substantially improves model performance. Relative to QRISK3, the best performing models improved the discrimination by 3.78% and improved precision by 1.80%. (ii) Both model- and data-centric approaches are necessary to improve predictive performance. The benefits of using a comprehensive history of diseases were far more pronounced when a neural sequence model, BEHRT, was used. This highlights the importance of the temporality of medical events that existing clinical risk models fail to capture. (iii) Besides the history of diseases, socioeconomic factors and measurements had small but significant independent contributions to the predictive performance. Conclusion: These findings emphasize the need for considering broad determinants and novel modelling approaches to enhance CVD incidence prediction.

Osmotically evoked PLCδ1-dependent translocation of ΔN-TRPV1 channels in rat supraoptic neurons.

Osmoregulation is an essential homeostatic process that requires constant release of vasopressin during sustained increases in plasma osmolality. The magnocellular neurosecretory cells (MNCs) respond to increases in external osmolality through increases in the activity of ΔN-TRPV1 channels, which leads to increased action potential firing and vasopressin release. We show that sustained exposure of acutely isolated rat and mouse MNCs to hypertonic solutions (90 min) causes a reversible translocation of ΔN-TRPV1 channels from internal stores to the plasma membrane that depends on the activation of phospholipase C and on SNARE-dependent exocytosis. ΔN-TRPV1 channel translocation is absent in MNCs isolated from transgenic mice lacking the PLCδ1 isoform, suggesting that PLCδ1 is essential for triggering this process. The translocation of ΔN-TRPV1 channels to the cell surface could contribute to the maintenance of MNC excitability during sustained increases in osmolality. Our data therefore have important implications for the mechanisms underlying mammalian osmoregulation.

Nutrient limitation of phytoplankton in three tributaries of Chesapeake Bay: Detecting responses following nutrient reductions.

Many coastal ecosystems suffer from eutrophication, algal blooms, and dead zones due to excessive anthropogenic inputs of nitrogen (N) and phosphorus (P). This has led to regional restoration efforts that focus on managing watershed loads of N and P. In Chesapeake Bay, the largest estuary in the United States, dual nutrient reductions of N and P have been pursued since the 1980s. However, it remains unclear whether nutrient limitation - an indicator of restriction of algal growth by supplies of N and P - has changed in the tributaries of Chesapeake Bay following decades of reduction efforts. Toward that end, we analyzed historical data from nutrient-addition bioassay experiments and data from the Chesapeake Bay long-term water-quality monitoring program for six stations in three tidal tributaries (i.e., Patuxent, Potomac, and Choptank Rivers). Classification and regression tree (CART) models were developed using concurrent collections of water-quality parameters for each bioassay monitoring location during 1990-2003, which satisfactorily predicted the bioassay-based measures of nutrient limitation (classification accuracy = 96%). Predictions from the CART models using water-quality monitoring data showed enhanced nutrient limitation over the period of 1985-2020 at four of the six stations, including the downstream station in each of these three tributaries. These results indicate detectable, long-term water-quality improvements in the tidal tributaries. Overall, this research provides a new analytical tool for detecting signs of ecosystem recovery following nutrient reductions. More broadly, the approach can be adapted to other waterbodies with long-term bioassays and water-quality data sets to detect ecosystem recovery.

Burnout and Turnover Intention Among Peer Providers and Other Providers of Mental Health Services in a Rural Two-County Area.

Peer providers in the mental health field, having their own lived experience with mental illness, use their personal experience to assist the consumers of their services. Given high burnout rates in the mental health field, there have been two prior investigations of burnout among peer providers. The present study extends those prior investigations to a sample of peer providers working in community mental health programs in a rural area of the United States. Consistent with the prior studies, there were no differences in burnout between peer providers and other providers employed by those programs, with particularly strong support for the null hypothesis regarding the emotional exhaustion component of burnout. There were also no differences in strength of turnover intentions. However, among the non-consumer providers emotional exhaustion was correlated with both types of turnover intention assessed in this study (intent to change job setting within the mental health field and intent to leave the mental health workforce), whereas among the peer providers emotional exhaustion was correlated only with intent to leave the mental health field. Workload dissatisfaction was the workplace variable most strongly associated with emotional exhaustion among both types of providers. Other moderately strong inverse predictors of emotional exhaustion among peer providers were workplace community and workplace control, and the correlation between emotional exhaustion and workplace control was significantly stronger among the peer providers than among the other providers.

Routine postoperative noninvasive respiratory support and pneumonia after elective surgery: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Postoperative pulmonary complications, including pneumonia, are a substantial cause of morbidity. We hypothesised that routine noninvasive respiratory support was associated with a lower incidence of pneumonia after surgery. METHODS: Systematic review and meta-analysis of RCTs comparing the routine use of continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or high-flow nasal oxygen (HFNO) against standard postoperative care in the adult population. We searched MEDLINE (PubMed), EMBASE, and CENTRAL from the start of indexing to July 27, 2021. Articles were reviewed and data extracted in duplicate, with discrepancies resolved by a senior investigator. The primary outcome was pneumonia, and the secondary outcome was postoperative pulmonary complications. We calculated risk difference (RD) with 95% confidence intervals using DerSimonian and Laird random effects models. We assessed risk of bias using the Cochrane risk of bias tool. RESULTS: From 18 513 records, we included 38 trials consisting of 9782 patients. Pneumonia occurred in 214/4403 (4.9%) patients receiving noninvasive respiratory support compared with 216/3937 (5.5%) receiving standard care (RD -0.01 [95% confidence interval: -0.02 to 0.00]; I2=8%; P=0.23). Postoperative pulmonary complications occurred in 393/1379 (28%) patients receiving noninvasive respiratory support compared with 280/902 (31%) receiving standard care (RD -0.11 [-0.23 to 0.01]; I2=79%; P=0.07). Subgroup analyses did not identify a benefit of CPAP, NIV, or HFNO in preventing pneumonia. Tests for publication bias suggest six unreported trials. CONCLUSION: The results of this evidence synthesis do not support the routine use of postoperative CPAP, NIV, or HFNO to prevent pneumonia after surgery in adults. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42019156741.

Determinants of Telerehabilitation Acceptance among Patients Attending Pulmonary Rehabilitation Programs in the United States.

BACKGROUND: Pulmonary rehabilitation (PR) is an interdisciplinary intervention designed to improve the physical status and the psychological condition of people with chronic respiratory diseases. To improve patients' participation in PR programs, telerehabilitation has been introduced. OBJECTIVE: This study aimed to identify factors that could influence the intention to use telerehabilitation among patients attending traditional PR programs. METHODS: This cross-sectional study recruited subjects attending the PR centers in the hospitals of the Indiana State University, United States of America, between January and May 2017. Data were collected using self-administered Tele-Pulmonary Rehabilitation Acceptance Scale (TPRAS). TPRAS had two subscales: perceived usefulness and perceived ease of use. Behavioral intention (BI) was the dependent variable, and all responses were dichotomized into positive and negative intention to use. Multiple logistic regressions were performed to assess the influence of variables on the intention to use telerehabilitation. RESULTS: A total of 134 respondents were included in this study, of which 61.2% indicated positive intention to use telerehabilitation. Perceived usefulness was a significant predictor of the positive intentions to use of telerehabilitation. Duration of respiratory disease was negatively associated with the use of telerehabilitation. CONCLUSION: Perceived usefulness was a significant predictor of using telerehabilitation. The findings of this study may be useful for health-care organizations in improving the adoption of telerehabilitation or in its implementation. Future telerehabilitation acceptance studies could explore the effects of additional factors including computer literacy and culture on the intention to use telerehabilitation.

Identifying sensitive windows of airborne lead exposure associated with behavioral outcomes at age 12.

Despite the precipitous decline of airborne lead concentrations following the removal of lead in gasoline, lead is still detectable in ambient air in most urban areas. Few studies, however, have examined the health effects of contemporary airborne lead concentrations in children. METHODS: We estimated monthly air lead exposure among 263 children (Cincinnati Childhood Allergy and Air Pollution Study; Cincinnati, OH; 2001-2005) using temporally scaled predictions from a validated land use model and assessed neurobehavioral outcomes at age 12 years using the parent-completed Behavioral Assessment System for Children, 2nd edition. We used distributed lag models to estimate the effect of airborne lead exposure on behavioral outcomes while adjusting for potential confounding by maternal education, community-level deprivation, blood lead concentrations, greenspace, and traffic related air pollution. RESULTS: We identified sensitive windows during mid- and late childhood for increased anxiety and atypicality scores, whereas sensitive windows for increased aggression and attention problems were identified immediately following birth. The strongest effect was at age 12, where a 1 ng/m3 increase in airborne lead exposure was associated with a 3.1-point (95% confidence interval: 0.4, 5.7) increase in anxiety scores. No sensitive windows were identified for depression, somatization, conduct problems, hyperactivity, or withdrawal behaviors. CONCLUSIONS: We observed associations between exposure to airborne lead concentrations and poor behavioral outcomes at concentrations 10 times lower than the National Ambient Air Quality Standards set by the US Environmental Protection Agency.

PLCδ1 Plays Central Roles in the Osmotic Activation of ΔN-TRPV1 Channels in Mouse Supraoptic Neurons and in Murine Osmoregulation.

The magnocellular neurosecretory cells (MNCs) of the hypothalamus play a vital role in osmoregulation, but the mechanisms underlying MNC osmosensitivity are not fully understood. We showed previously that high osmolality activates phospholipase C (PLC) in rat MNCs in a Ca2+-dependent manner and that PLC activation is necessary for full osmotic activation of an N-terminal variant of the TRPV1 (ΔN-TRPV1) channel. We therefore hypothesized that the Ca2+-dependent δ1 isoform of PLC contributes to ΔN-TRPV1 activation and tested whether MNC function is defective in a transgenic PLCδ1 KO mouse. Water deprivation for 24 h caused greater increases in serum osmolality and losses in body weight in PLCδ1 KO mice than it did in control mice. Action potentials and ΔN-TRPV1 currents were measured in acutely isolated mouse MNCs using whole-cell patch clamp before and after exposure to hypertonic solutions. This treatment elicited a significant activation of ΔN-TRPV1 currents and an increase in firing rate in MNCs isolated from control mice, but not from PLCδ1 KO mice. Submembranous filamentous actin was measured in isolated MNCs before and after treatment with angiotensin II and hypertonic solution. Both treatments caused an increase in filamentous actin fluorescence in MNCs isolated from control mice, but both responses were significantly attenuated in MNCs from PLCδ1 KO mice. Our data demonstrate that the PLCδ1 isoform plays a key role in the activation of ΔN-TRPV1 channels and in osmosensory transduction in MNCs. This study advances our understanding of the molecular mechanisms underlying mammalian osmoregulation.SIGNIFICANCE STATEMENT Magnocellular neurosecretory cells (MNCs) of the hypothalamus play a central role in osmoregulation. We have identified a key role for the PLCδ1 isoform in the activation of ΔN-TRPV1 channels and osmosensory transduction in MNCs. The data indicate that the PLCδ1 isoform is activated by the Ca2+ influx occurring during MNC action potentials and exerts a positive feedback on ΔN-TRPV1 channels to enhance MNC excitability. This study provides evidence that PLCδ1 is a key molecule underlying osmosensory transduction, the regulation of VP release, and osmoregulation.

Hemodynamic Assay of Hind Limb in Multiple Animal Models.

INTRODUCTION: Measuring hemodynamic characteristics of injured limbs is paramount to early identification of potentially damaging ischemic conditions, but can often prove difficult attributable to a multitude of factors. Here, we present an in vivo optical imaging technique to characterize pulsatile blood flow quality through the distal extremity in multiple animal models that replicate the signs of distal extremity ischemia. The purpose of this study is to examine the feasibility of the optical imaging technique and relevance to hemodynamic complications such as acute compartment syndrome (ACS) and nonobvious hemorrhage. MATERIALS AND METHODS: In one pig and six mice, three different methods were used to create ischemic conditions in the lower extremity, producing symptoms similar to what is observed in ACS. In each condition, perfusion to the distal extremity was measured with the hemodynamic detection device (HDD; Odin Technologies), an optical assessment tool for perfusion and blood flow quality. RESULTS: We observed a profound decrease in extremity perfusion immediately after onset of ischemia in all three models. In the porcine model, the HDD's measurements demonstrated similar characteristic flow between the various measurement locations. After the tourniquet was applied, the HDD revealed a 95% decrease in normalized perfusion value (npv) while the intracompartmental pressure rose from 5 to 52 mmHg (a 47mmHg increase). After the tourniquet was removed during reperfusion, the normalized blood flow returned to baseline and the intracompartmental pressure dropped from 20 to 6 mmHg in less than 5 minutes. For each mouse, the HDD test leg demonstrated a measurement of 0.97 npv before femoral ligation and 0.05 npv after femoral ligation, an 89% decrease (P < .01) in flow. Pulsed-wave Doppler ultrasound (PWDU) measurements on the test leg had pre-ligation measurement of 0.84 npv and a post-ligation measurement of 0.001 npv, a 99% decrease. These PWDU measurements revealed almost complete stoppage of blood flow during ischemia, followed by a substantial increase after the femoral artery ligation was removed. CONCLUSIONS: Here, we show that a novel, optics-based sensing system can be used to diagnose and assess ACS in animal models. This technology is comparable to other standards used to monitor ACS and nonobvious hemorrhage and may also be a plausible alternative to prolonged invasive monitoring of patients with sustained extremity trauma.

Testing for correlation between two time series using a parametric bootstrap.

We study the problem of determining if two time series are correlated in the mean and variance. Several test statistics, originally designed for determining the correlation between two mean processes or goodness-of-fit testing, are explored and formally introduced for determining cross-correlation in variance. Simulations demonstrate the theoretical asymptotic distribution can be ineffective in finite samples. Parametric bootstrapping is shown to be an effective tool in such an enterprise. A large simulation study is provided demonstrating the efficacy of the bootstrapping method. Lastly, an empirical example explores a correlation between the Standard & Poor's 500 index and the Euro/US dollar exchange rate while also demonstrating a level of robustness for the proposed method.

Client buy-in: An essential consideration for graded motor imagery in hand therapy.

STUDY DESIGN: This is a cross-sectional survey research. INTRODUCTION: Current evidence provides efficacy of graded motor imagery (GMI) in chronic pain conditions but also reveals barriers to its implementation. PURPOSE OF THE STUDY: The purpose of this study was to describe current utilization of GMI in hand therapy practice. METHODS: Survey tool, informed by literature and Revised Neurophysiology of Pain Questionnaire (NPQ) was electronically distributed to members of the American Society of Hand Therapists. RESULTS: 132 therapists completed the survey. 65.2% reported they would always or very likely use GMI in clients with central sensitization, but no relationship between the likelihood of therapists using GMI to score achieved on the NPQ was found. Lack of patient buy-in, was the main barrier cited. "Sell it well" with pain neuroscience education the most cited strategy. DISCUSSION: GMI is frequently used in clients with central sensitization but requires client buy-in. CONCLUSIONS: Understanding and explaining pain mechanism is essential for implementing GMI.

Nutrient limitation of phytoplankton in Chesapeake Bay: Development of an empirical approach for water-quality management.

Understanding the temporal and spatial roles of nutrient limitation on phytoplankton growth is necessary for developing successful management strategies. Chesapeake Bay has well-documented seasonal and spatial variations in nutrient limitation, but it remains unknown whether these patterns of nutrient limitation have changed in response to nutrient management efforts. We analyzed historical data from nutrient bioassay experiments (1992-2002) and data from long-term, fixed-site water-quality monitoring program (1990-2017) to develop empirical approaches for predicting nutrient limitation in the surface waters of the mainstem Bay. Results from classification and regression trees (CART) matched the seasonal and spatial patterns of bioassay-based nutrient limitation in the 1992-2002 period much better than two simpler, non-statistical approaches. An ensemble approach of three selected CART models satisfactorily reproduced the bioassay-based results (classification rate = 99%). This empirical approach can be used to characterize nutrient limitation from long-term water-quality monitoring data on much broader geographic and temporal scales than would be feasible using bioassays, providing a new tool for informing water-quality management. Results from our application of the approach to 21 tidal monitoring stations for the period of 2007-2017 showed modest changes in nutrient limitation patterns, with expanded areas of nitrogen-limitation and contracted areas of nutrient saturation (i.e., not limited by nitrogen or phosphorus). These changes imply that long-term reductions in nitrogen load have led to expanded areas with nutrient-limited phytoplankton growth in the Bay, reflecting long-term water-quality improvements in the context of nutrient enrichment. However, nutrient limitation patterns remain unchanged in the majority of the mainstem, suggesting that nutrient loads should be further reduced to achieve a less nutrient-saturated ecosystem.

Correction: Dissolved organic matter protects mosquito larvae from damaging solar UV radiation.

[This corrects the article DOI: 10.1371/journal.pone.0240261.].

Methacholine-Induced Cough in the Absence of Asthma: Insights From Impulse Oscillometry.

INTRODUCTION: The pathophysiologic differences between methacholine-induced cough but normal airway sensitivity (COUGH) and healthy individuals (CONTROL) are incompletely understood and may be due to differences in the bronchodilating effect of deep inspirations (DIs). The purpose of this study is to compare the bronchodilating effect of DIs in individuals with classic asthma (CA), cough variant asthma (CVA), and COUGH with CONTROL and to assess impulse oscillometry (IOS) measures as predictors of the bronchodilating effect of DIs. METHODS: A total of 43 adults [18 female; 44.8 ± 12.3 years (mean ± SD); n = 11 CA, n = 10 CVA, n = 7 COUGH, n = 15 CONTROL] underwent modified high-dose methacholine challenge, with IOS and partial/maximal expiratory flow volume (PEFV/MEFV) maneuvers (used to calculate DI Index) to a maximum change (Δ) in FEV1 of 50% from baseline (MAX). Cough count and dyspnea were measured at each dose. The relation between IOS parameters and DI Index was assessed at baseline and MAX using multivariable linear regression analysis. RESULTS: Cough frequency, dyspnea intensity, and baseline peripheral resistance (R5-R20) were significantly greater in COUGH compared with CONTROL (p = 0.006, p = 0.029, and p = 0.035, respectively). At MAX, the DI Index was significantly lower in COUGH (0.01 ± 0.36) compared with CA (0.67 ± 0.97, p = 0.008), CVA (0.51 ± 0.73, p = 0.012), and CONTROL (0.68 ± 0.45, p = 0.005). Fres and R5-R20 were independent IOS predictors of the DI Index. CONCLUSION: The bronchodilating effect is impaired in COUGH and preserved in mild CA, CVA, and CONTROL. Increased peripheral airway resistance and decreased resonant frequency are associated with a decreased DI Index. COUGH is a clinical phenotype distinct from healthy normals and asthma.