Multilayer Perceptron Neural Network Analysis of Fluoroscopic Working Angle on Transcatheter Aortic Valve Implantation Complications.

BACKGROUND: We sought to determine whether there is a relationship between the fluoroscopic working angle used to achieve a co-planar view during the deployment of the prosthesis during transcatheter aortic valve implantation (TAVI) and rates of complications, including paravalvular leaks, complete heart block, annular rupture, stroke, valve embolization, discharge to a skilled nursing facility and death within thirty days. METHODS: All patients undergoing TAVI at our institution from 2015 to 2022 were retrospectively analyzed. Images were reviewed to determine the fluoroscopic working angle during deployment, and medical records were used to determine the incidence and type of complication. A multilayer perceptron was employed to evaluate the predictive ability of the fluoroscopic working angle during deployment on complications of one-day and 30-day paravalvular leak, 30-day mortality, the need for a new pacemaker, discharge to a skilled nursing facility, stroke and the requirement for emergency intervention. RESULTS: Eight hundred and thirty-four patients were included in the study. Fluoroscopic working angle had excellent predictive value for stroke (area under the receiver operating characteristic curve (AUROC) of 0.812), one-day (AUROC 0.850), and 30-day paravalvular leak (AUROC 0.801). However, feature importance and scaled weighting analysis indicated that only a working angle in the left anterior oblique/cranial quadrant was informative for the development of an outcome of interest specific to a working angle quadrant (30-day paravalvular leak). CONCLUSION: Fluoroscopic working angle may be a useful way to further refine well-established risk calculi during TAVI.

Temperature-Dependent Evaporative Anthropogenic VOC Emissions Significantly Exacerbate Regional Ozone Pollution.

The evaporative emissions of anthropogenic volatile organic compounds (AVOCs) are sensitive to ambient temperature. This sensitivity forms an air pollution-meteorology connection that has not been assessed on a regional scale. We parametrized the temperature dependence of evaporative AVOC fluxes in a regional air quality model and evaluated the impacts on surface ozone in the Beijing-Tianjin-Hebei (BTH) area of China during the summer of 2017. The temperature dependency of AVOC emissions drove an enhanced simulated ozone-temperature sensitivity of 1.0 to 1.8 µg m-3 K-1, comparable to the simulated ozone-temperature sensitivity driven by the temperature dependency of biogenic VOC emissions (1.7 to 2.4 µg m-3 K-1). Ozone enhancements driven by temperature-induced AVOC increases were localized to their point of emission and were relatively more important in urban areas than in rural regions. The inclusion of the temperature-dependent AVOC emissions in our model improved the simulated ozone-temperature sensitivities on days of ozone exceedance. Our results demonstrated the importance of temperature-dependent AVOC emissions on surface ozone pollution and its heretofore unrepresented role in air pollution-meteorology interactions.

Overview of the Alaskan Layered Pollution and Chemical Analysis (ALPACA) Field Experiment.

The Alaskan Layered Pollution And Chemical Analysis (ALPACA) field experiment was a collaborative study designed to improve understanding of pollution sources and chemical processes during winter (cold climate and low-photochemical activity), to investigate indoor pollution, and to study dispersion of pollution as affected by frequent temperature inversions. A number of the research goals were motivated by questions raised by residents of Fairbanks, Alaska, where the study was held. This paper describes the measurement strategies and the conditions encountered during the January and February 2022 field experiment, and reports early examples of how the measurements addressed research goals, particularly those of interest to the residents. Outdoor air measurements showed high concentrations of particulate matter and pollutant gases including volatile organic carbon species. During pollution events, low winds and extremely stable atmospheric conditions trapped pollution below 73 m, an extremely shallow vertical scale. Tethered-balloon-based measurements intercepted plumes aloft, which were associated with power plant point sources through transport modeling. Because cold climate residents spend much of their time indoors, the study included an indoor air quality component, where measurements were made inside and outside a house to study infiltration and indoor sources. In the absence of indoor activities such as cooking and/or heating with a pellet stove, indoor particulate matter concentrations were lower than outdoors; however, cooking and pellet stove burns often caused higher indoor particulate matter concentrations than outdoors. The mass-normalized particulate matter oxidative potential, a health-relevant property measured here by the reactivity with dithiothreiol, of indoor particles varied by source, with cooking particles having less oxidative potential per mass than pellet stove particles.

MRI-predicted extramural vascular invasion and tumour deposit are main predictors of disease-free survival in patients undergoing surgical resection for rectal cancer.

BACKGROUND: MRI is crucial in staging patients with rectal cancer and planning treatment. The aim was to analyse the prognostic role of MRI-predicted tumour deposits and/or extramural vascular invasion (mrTD/EMVI) in a cohort of patients with rectal cancer undergoing surgical resection, with selective neoadjuvant chemoradiotherapy (nCRT). METHOD: Retrospective analysis of a single-centre cohort of consecutive patients with rectal cancer undergoing low anterior resection or abdominoperineal excision between 2008 and 2020. Unit policy was selective nCRT for MRI-predicted threatened or involved circumferential resection margin (mrCRM), or radiologically involved pelvic sidewall nodes. The primary outcome was disease-free survival. Secondary outcomes were rates of local recurrence, distant recurrence and overall survival. RESULTS: A total of 314 patients were analysed. Median age was 65 years (female/male: 114/200). A total of 54/314 (17%) had nCRT and 35 patients (11%) underwent abdominoperineal excision. Median follow-up was 64 months. Overall, local recurrence was detected in 18/314 (5.7%) and distant recurrence in 45/314 (14.3%). In patients not receiving nCRT (n = 260), local recurrence was detected in 11/260 (4.2%) and distant recurrence in 35/260 (13.5%). Disease-free survival was 80.5% at 5 years. Specifically, disease-free survival was 89% in mrTD/EMVI-negative and mrCRM-negative, 67% in mrTD/EMVI-positive and mrCRM-negative, and 64% in the mrCRM-positive rectal cancer (log-rank, P < 0.001). On multivariable Cox-regression analysis mrTD/EMVI was the only MRI variable associated with disease-free survival (hazard ratio 2.95; P < 0.001). CONCLUSION: mrTD/EMVI is a major prognostic indicator. Rectal cancer patients with mrCRM-negative and mrTD/EMVI-negative have excellent long-term outcomes with surgery alone. Patients with mrTD/EMVI-positive should be selectively stratified for neoadjuvant treatments in future clinical trials.

Successful aging after elective surgery II: Study design and methods.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II study was designed to increase knowledge of the pathophysiology and linkages between delirium and dementia. We examine novel biomarkers potentially associated with delirium, including inflammation, Alzheimer's disease (AD) pathology and neurodegeneration, neuroimaging markers, and neurophysiologic markers. The goal of this paper is to describe the study design and methods for the SAGES II study. METHODS: The SAGES II study is a 5-year prospective observational study of 400-420 community dwelling persons, aged 65 years and older, assessed prior to scheduled surgery and followed daily throughout hospitalization to observe for development of delirium and other clinical outcomes. Delirium is measured with the Confusion Assessment Method (CAM), long form, after cognitive testing. Cognitive function is measured with a detailed neuropsychologic test battery, summarized as a weighted composite, the General Cognitive Performance (GCP) score. Other key measures include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS)/electroencephalography (EEG), and Amyloid positron emission tomography (PET) imaging. We describe the eligibility criteria, enrollment flow, timing of assessments, and variables collected at baseline and during repeated assessments at 1, 2, 6, 12, and 18 months. RESULTS: This study describes the hospital and surgery-related variables, delirium, long-term cognitive decline, clinical outcomes, and novel biomarkers. In inter-rater reliability assessments, the CAM ratings (weighted kappa = 0.91, 95% confidence interval, CI = 0.74-1.0) in 50 paired assessments and GCP ratings (weighted kappa = 0.99, 95% CI 0.94-1.0) in 25 paired assessments. We describe procedures for data quality assurance and Covid-19 adaptations. CONCLUSIONS: This complex study presents an innovative effort to advance our understanding of the inter-relationship between delirium and dementia via novel biomarkers, collected in the context of major surgery in older adults. Strengths include the integration of MRI, TMS/EEG, PET modalities, and high-quality longitudinal data.

Mitigating the impact of air pollution on dementia and brain health: Setting the policy agenda.

BACKGROUND: Emerging research suggests exposure to high levels of air pollution at critical points in the life-course is detrimental to brain health, including cognitive decline and dementia. Social determinants play a significant role, including socio-economic deprivation, environmental factors and heightened health and social inequalities. Policies have been proposed more generally, but their benefits for brain health have yet to be fully explored. OBJECTIVE AND METHODS: Over the course of two years, we worked as a consortium of 20+ academics in a participatory and consensus method to develop the first policy agenda for mitigating air pollution's impact on brain health and dementia, including an umbrella review and engaging 11 stakeholder organisations. RESULTS: We identified three policy domains and 14 priority areas. Research and Funding included: (1) embracing a complexities of place approach that (2) highlights vulnerable populations; (3) details the impact of ambient PM2.5 on brain health, including current and historical high-resolution exposure models; (4) emphasises the importance of indoor air pollution; (5) catalogues the multiple pathways to disease for brain health and dementia, including those most at risk; (6) embraces a life course perspective; and (7) radically rethinks funding. Education and Awareness included: (8) making this unrecognised public health issue known; (9) developing educational products; (10) attaching air pollution and brain health to existing strategies and campaigns; and (11) providing publicly available monitoring, assessment and screening tools. Policy Evaluation included: (12) conducting complex systems evaluation; (13) engaging in co-production; and (14) evaluating air quality policies for their brain health benefits. CONCLUSION: Given the pressing issues of brain health, dementia and air pollution, setting a policy agenda is crucial. Policy needs to be matched by scientific evidence and appropriate guidelines, including bespoke strategies to optimise impact and mitigate unintended consequences. The agenda provided here is the first step toward such a plan.

A nationwide study on the adoption and short-term outcomes of transanal total mesorectal excision in the UK.

BACKGROUND: The interest and adoption of transanal total mesorectal excision (TaTME) is growing worldwide, but evidence on nationwide implementation and short-term outcomes is scarce. This study aims to evaluate national results for this relatively new technique in the UK. METHODS: All TaTME procedures performed in the UK and recorded on the international TaTME registry between January 2013 and January 2018 were analyzed. Surgeons who received training on TaTME in the UK were sent a survey regarding their experience with implementation of TaTME in their unit. Primary endpoint was a composite for "optimal pathology" (free resection margin (R0) and TME specimen with no major defects and no rectal wall perforations). Secondary outcomes included 30-day clinical course and survey outcomes. RESULTS: Forty-two hospitals entered 513 cases over a 5-year period; 28 of 42 hospitals (66.7%) performed ten cases or less. The indication for surgery was cancer in 364 (71.0%) cases. Optimal pathology was achieved in 295 (92.8%), with an involved resection margin (R1) rate of 13 of 513 (4.1%). A Clavien-Dindo ≥III within 30 days was 13.4% (N.=45) and 6.8% (N.=10) in the cancer and benign groups, respectively. Based on the survey (response rate 68 of 86; 79%), 76.1% of the surgeons implemented TaTME in their unit after receiving training, all of whom experienced difficulties with performing TaTME. CONCLUSIONS: This study reports acceptable nationwide short-term outcomes of TaTME. However, adoption occurred in a rapid and non-standardized manner. A structured TaTME training program is therefore recommended.

Have Synergies Between Nitrogen Deposition and Atmospheric CO2 Driven the Recent Enhancement of the Terrestrial Carbon Sink?

The terrestrial carbon sink has increased since the turn of this century at a time of increased fossil fuel burning, yet the mechanisms enhancing this sink are not fully understood. Here we assess the hypothesis that regional increases in nitrogen deposition since the early 2000s has alleviated nitrogen limitation and worked in tandem with enhanced CO2 fertilization to increase ecosystem productivity and carbon sequestration, providing a causal link between the parallel increases in emissions and the global land carbon sink. We use the Community Land Model (CLM4.5-BGC) to estimate the influence of changes in atmospheric CO2, nitrogen deposition, climate, and their interactions to changes in net primary production and net biome production. We focus on two periods, 1901-2016 and 1990-2016, to estimate changes in land carbon fluxes relative to historical and contemporary baselines, respectively. We find that over the historical period, nitrogen deposition (14%) and carbon-nitrogen synergy (14%) were significant contributors to the current terrestrial carbon sink, suggesting that long-term increases in nitrogen deposition led to a substantial increase in CO2 fertilization. However, relative to the contemporary baseline, changes in nitrogen deposition and carbon-nitrogen synergy had no substantial contribution to the 21st century increase in global carbon uptake. Nonetheless, we find that increased nitrogen deposition in East Asia since the early 1990s contributed 50% to the overall increase in net biome production over this region, highlighting the importance of carbon-nitrogen interactions. Therefore, potential large-scale changes in nitrogen deposition could have a significant impact on terrestrial carbon cycling and future climate.

Incidence and Risk Factors for Anastomotic Failure in 1594 Patients Treated by Transanal Total Mesorectal Excision: Results From the International TaTME Registry.

OBJECTIVE: To determine the incidence of anastomotic-related morbidity following Transanal Total Mesorectal Excision (TaTME) and identify independent risk factors for failure. BACKGROUND: Anastomotic leak and its sequelae are dreaded complications following gastrointestinal surgery. TaTME is a recent technique for rectal resection, which includes novel anastomotic techniques. METHODS: Prospective study of consecutive reconstructed TaTME cases recorded over 30 months in 107 surgical centers across 29 countries. Primary endpoint was "anastomotic failure," defined as a composite endpoint of early or delayed leak, pelvic abscess, anastomotic fistula, chronic sinus, or anastomotic stricture. Multivariate regression analysis performed identifying independent risk factors of anastomotic failure and an observed risk score developed. RESULTS: One thousand five hundred ninety-four cases with anastomotic reconstruction were analyzed; 96.6% performed for cancer. Median anastomotic height from anal verge was 3.0 ±â€Š2.0 cm with stapled techniques accounting for 66.0%. The overall anastomotic failure rate was 15.7%. This included early (7.8%) and delayed leak (2.0%), pelvic abscess (4.7%), anastomotic fistula (0.8%), chronic sinus (0.9%), and anastomotic stricture in 3.6% of cases. Independent risk factors of anastomotic failure were: male sex, obesity, smoking, diabetes mellitus, tumors >25 mm, excessive intraoperative blood loss, manual anastomosis, and prolonged perineal operative time. A scoring system for preoperative risk factors was associated with observed rates of anastomotic failure between 6.3% to 50% based on the cumulative score. CONCLUSIONS: Large tumors in obese, diabetic male patients who smoke have the highest risk of anastomotic failure. Acknowledging such risk factors can guide appropriate consent and clinical decision-making that may reduce anastomotic-related morbidity.

Basin-Scale Observations of Monoterpenes in the Arctic and Atlantic Oceans.

We report novel in situ speciated observations of monoterpenes (α- and ß-pinene, myrcene, δ3-carene, ocimene, limonene) in seawater and air during three cruises in the Arctic and Atlantic Oceans, in/over generally oligotrophic waters. Oceanic concentrations of the individual monoterpenes ranged from below the detection limit of <1 pmol L-1 to 5 pmol L-1, with average concentrations of between 0.5 and 2.9 pmol L-1. After careful filtering for contamination, atmospheric mixing ratios varied from below the detection limit (<1 pptv) to 5 pptv, with averages of 0.05-5 pptv; these levels are up to 2 orders of magnitude lower than those reported previously. This could be at least partly due to sampling over waters with much lower biological activity than in previous studies. Unlike in previous studies, no clear relationships of the monoterpenes with biological variables were found. Based on our measured seawater concentrations and a global model simulation, we estimate total global marine monoterpene emissions of 0.16 Tg C yr-1, similar to a previous bottom-up estimate based on laboratory monoculture studies but 2 orders of magnitude lower than a previous top-down estimate of 29.5 Tg C yr-1.

Analysis of Novel Interactions between Components of the Selenocysteine Biosynthesis Pathway, SEPHS1, SEPHS2, SEPSECS, and SECp43.

In mammalian cells, the incorporation of the 21st amino acid, selenocysteine, into proteins is guided by the Sec machinery. The function of this protein complex requires several protein-protein and protein-RNA interactions, leading to the incorporation of selenocysteine at UGA codons. It is guided by stem-loop structures localized in the 3' untranslated regions of the selenoprotein-encoding genes. Here, we conducted a global analysis of interactions between the Sec biosynthesis and incorporation components using a bioluminescence resonance energy transfer assay in mammalian cells that showed that selenocysteine synthase (SEPSECS), SECp43, and selenophosphate synthetases SEPHS1 and SEPHS2 form oligomers in eukaryotic cells. We also showed that SEPHS2 interacts with SEPSECS and SEPHS1; these interactions were confirmed by co-immunoprecipitation. To further analyze the interactions of SECp43, the protein was expressed in Escherichia coli, and small-angle X-ray scattering analysis revealed that it is a globular protein comprising two RNA-binding domains. Using phage display, we identified potential interaction sites and highlighted two residues (K166 and P167) required for its dimerization. The SECp43 structural model presented here constitutes the basis of future exploration of the protein-protein interactions among early components of the selenocysteine biosynthesis and incorporation pathway.

Transanal Total Mesorectal Excision: International Registry Results of the First 720 Cases.

OBJECTIVE: This study aims to report short-term clinical and oncological outcomes from the international transanal Total Mesorectal Excision (taTME) registry for benign and malignant rectal pathology. BACKGROUND: TaTME is the latest minimally invasive transanal technique pioneered to facilitate difficult pelvic dissections. Outcomes have been published from small cohorts, but larger series can further assess the safety and efficacy of taTME in the wider surgical population. METHODS: Data were analyzed from 66 registered units in 23 countries. The primary endpoint was "good-quality TME surgery." Secondary endpoints were short-term adverse events. Univariate and multivariate regression analyses were used to identify independent predictors of poor specimen outcome. RESULTS: A total of 720 consecutively registered cases were analyzed comprising 634 patients with rectal cancer and 86 with benign pathology. Approximately, 67% were males with mean BMI 26.5 kg/m. Abdominal or perineal conversion was 6.3% and 2.8%, respectively. Intact TME specimens were achieved in 85%, with minor defects in 11% and major defects in 4%. R1 resection rate was 2.7%. Postoperative mortality and morbidity were 0.5% and 32.6% respectively. Risk factors for poor specimen outcome (suboptimal TME specimen, perforation, and/or R1 resection) on multivariate analysis were positive CRM on staging MRI, low rectal tumor <2 cm from anorectal junction, and laparoscopic transabdominal posterior dissection to <4 cm from anal verge. CONCLUSIONS: TaTME appears to be an oncologically safe and effective technique for distal mesorectal dissection with acceptable short-term patient outcomes and good specimen quality. Ongoing structured training and the upcoming randomized controlled trials are needed to assess the technique further.

GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.

Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and Aß42 are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10⁻9 for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10⁻8 and p = 3.22 × 10⁻9 for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10⁻8 for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10⁻4, 0.039, 4.86 × 10⁻5, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci.

One round of SELEX for the generation of DNA aptamers directed against KLK6.

Kallikrein-related peptidase 6 (KLK6) is an active serine protease that has been implicated in common pathologies, including neurodegenerative disorders such as Parkinson and Alzheimer disease and certain types of cancer. Antibodies, either polyclonal or monoclonal, that exhibit specificity for distinct members of the extended kallikrein family, including KLK6, were developed. With the exception of KLK3/PSA, the identification and generation of aptamers, as potential new tools with improved characteristics demanded for therapeutic and diagnostic applications, has not been explored for KLKs. Here, we report for the first time the identification of novel DNA aptamers against KLK6 that were isolated using a modified systemic evolution of ligands by exponential enrichment technique. The identified aptamers were characterized using fluorescence spectroscopy, competition ELISA, and quartz crystal microbalance, and two aptamers (008 and 022) were found to exhibit high affinity (K(d) in the low nanomolar range) for KLK6. Aptamers were tested for their ability to bind to serum albumin, to demonstrate their specificity for their target, and the possible involvement of such proteins in the transport of aptamers into the bloodstream. The developed aptamers are expected to assist the development of novel diagnostic, biosensing, and therapeutic strategies.

Crops and climate change: progress, trends, and challenges in simulating impacts and informing adaptation.

Assessments of the relationships between crop productivity and climate change rely upon a combination of modelling and measurement. As part of this review, this relationship is discussed in the context of crop and climate simulation. Methods for linking these two types of models are reviewed, with a primary focus on large-area crop modelling techniques. Recent progress in simulating the impacts of climate change on crops is presented, and the application of these methods to the exploration of adaptation options is discussed. Specific advances include ensemble simulations and improved understanding of biophysical processes. Finally, the challenges associated with impacts and adaptation research are discussed. It is argued that the generation of knowledge for policy and adaptation should be based not only on syntheses of published studies, but also on a more synergistic and holistic research framework that includes: (i) reliable quantification of uncertainty; (ii) techniques for combining diverse modelling approaches and observations that focus on fundamental processes; and (iii) judicious choice and calibration of models, including simulation at appropriate levels of complexity that accounts for the principal drivers of crop productivity, which may well include both biophysical and socio-economic factors. It is argued that such a framework will lead to reliable methods for linking simulation to real-world adaptation options, thus making practical use of the huge global effort to understand and predict climate change.

Private health plans perspectives: electronic personal health records and electronic prescribing.

BACKGROUND: Patients, payers, public health researchers, medical economists, and policymakers have all called for aggressive deployment of information technologies to support the management of health records and prescriptions. In response, payers of all types have been making investments in electronic systems. OBJECTIVES: To understand, analyze, and quantify current private payer involvement in electronic personal health records and electronic prescribing development and implementation. METHODS: A web-based survey involving 62 private commercial payer respondents representing more than 80 million covered lives and 16 national plans. RESULTS: Responses showed relatively high rates of implementation of electronic personal health records among respondents (20 currently and 9 in the next 24 months), but a unanimity of agreement of disappointing plan members' utilization of these systems. Implementation rates of electronic prescribing systems are even higher. More than half of the respondents reported utilization rates below 10%. CONCLUSION: The disappointing results with the implementations of electronic systems are most likely the result of variables exogenous to the technologies themselves. The low utilization of electronic prescribing is most likely related to the general lack of penetration of information technology into the work flow of most prescriber offices.

The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts.

Previously we have shown that the H1c haplotype on the background of the H1 clade of haplotypes at the MAPT locus is associated with increased risk for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease (AD). Here we replicated the association with AD in an additional autopsy confirmed series. We show that this haplotype increases both the expression of total MAPT transcript as well as specifically increasing the proportion of 4 microtubule binding repeat containing transcripts. We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies.

Uptake of ozone in human lungs and its relationship to local physiological response.

To investigate whether intersubject variations in the dose of inhaled ozone (O(3)) cause corresponding variations in the physiological response, 28 female and 32 male nonsmokers participated in a 1-h continuous inhalation of clean air or 0.25 ppm O(3) while exercising on a cycle ergometer at a constant ventilation rate of 30 L/min. The exposure protocols included continuous monitoring of respiratory flow rate and O(3) concentration from which O(3) uptake (OZU) and fractional uptake efficiency (UE) were computed. Pre-to-post changes in forced expired volume in 1 s (%DeltaFEV(1)), peripheral cross section for carbon dioxide diffusion (%Delta A(P)), and Fowler dead space volume (V(D)) were also measured for each exposure. Individual values of UE ranged from .70 to .98 among all the subjects, with significant differences (p<.05) existing between men and women. These intersubject differences were inversely correlated with breathing frequency and directly correlated with tidal volume. The mean +/- SD values of %Delta FEV(1), %Delta A(P), and %Delta V(D) were all significantly more negative in the O(3) exposure session (-13.31 +/- 13.40, -8.14 +/- 7.62, and -4.20 +/- 5.12, respectively) than in the air exposure session (-0.06 +/- 4.56, 0.22 +/- 10.82, and -0.70 +/- 6.88, respectively). Finally, our results showed that neither %DeltaFEV(1) nor %Delta V(D) was correlated OZU, whereas there was a significant relationship (rho = -0.325, p = .0257) between %Delta A(P) and OZU. We conclude that the overall uptake of O(3) is a weak predictor of intersubject variations in distal airspace response, but is not a predictor of intersubject variations in conducting airway responses.