bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactance and elastance as measures of small airways response to bronchodilator in asthma
Authors: Bhatawadekar S. A. , Leary D. , de Lange V. , Peters U. , Fulton S. , Hernandez P. , McParland C. , Maksym G. N. 
Published: October 2019

Bronchodilation alters both respiratory system resistance (Rrs) and reactance (Xrs) in asthma, but how changes in Rrs and Xrs compare, and respond differently in health and asthma, in reflecting the contributions from the large and small airways has not been assessed. We assessed reversibility using spirometry and oscillometry in healthy and asthma subjects. Using a multibranch airway-tree model with the mechanics of upper airway shunt, we compared the effects of airway dilation and small airways recruitment to explain the changes in Rrs and Xrs. Bronchodilator decreased Rrs by 23.0 (19.0)% in 18 asthma subjects and by 13.5 (19.5)% in 18 healthy subjects. Estimated respiratory system elastance (Ers) decreased by 23.2 (21.4)% in asthma, with no significant decrease in healthy subjects. With the use of the model, airway recruitment of 15% across a generation of the small airways could explain the changes in Ers in asthma with no recruitment in healthy subjects. In asthma, recruitment accounted for 40% of the changes in Rrs, with the remaining explained by airway dilation of 6.8% attributable largely to the central airways. Interestingly, the same dilation magnitude explained the changes in Rrs in healthy subjects. Shunt only affected Rrs of the model. Ers was unaltered in health and unaffected by shunt in both groups. In asthma, Ers changed comparably to Rrs and could be attributed to small airways, while the change in Rrs was split between large and small airways. This implies that in asthma Ers sensed through Xrs may be a more effective measure of small airways obstruction and recruitment than Rrs. NEW & NOTEWORTHY This is the first study to quantify to relative contributions of small and large airways to bronchodilator response in healthy subjects and patients with asthma. The response of the central airways to bronchodilator was similar in magnitude in both study groups, whereas the response of the small airways was significant among patients with asthma. These results suggest that low-frequency reactance and derived elastance are both sensitive measures of small airway function in asthma.
Relationship between Meat/Fish Consumption and Biliary Tract Cancer: The Japan Public Health Center–Based Prospective Study
Authors: Makiuchi Takeshi , Sobue Tomotaka , Kitamura Tetsuhisa , Ishihara Junko , Sawada Norie , Iwasaki Motoki , Yamaji Taiki , Shimazu Taichi , Tsugane Shoichiro 
Published: October 2019

AbstractBackground:The effect of meat and fish consumption on cancer risk has been well studied in humans. However, studies related to biliary tract cancer (BTC) are scarce.Methods:We examined the association between meat and fish consumption and the risk of BTC in a population-based prospective cohort study in Japan. HRs and 95% confidence intervals (CI) were estimated using the Cox proportional hazard model.Results:During 1995 and 1999, 43,177 men and 49,323 women ages 45 to 74 years were enrolled and followed up for 607,757.0 person-years (men) and 728,820.3 person-years (women) until 2012, during which time 217 male and 162 female BTC cases were identified. Higher total meat consumption was significantly associated with a decreased BTC risk in men (HR for the highest vs. lowest quartiles = 0.66; 95% CI, 0.44–0.98; Ptrend = 0.011) but not in women. Similar association was observed with red meat, but no association was observed with poultry. Fish was not associated with BTC risk. We further analyzed each BTC subtype to confirm the observed association with BTC. However, significant association with each BTC subtype was not observed, although a trend of decreased extrahepatic bile duct cancer risk was observed.Conclusions:BTC risk was lower among men who consumed more meat, particularly red meat, in Japan.Impact:This is the first prospective study that evaluated the relationship between meat and BTC. This may provide important suggestions to elucidate the etiology of BTC.
Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer
Authors: Whalen Kerry A. , White Brian H. , Quinn James M. , Kriksciukaite Kristina , Alargova Rossitza , Au Yeung Tsun P. , Bazinet Patrick , Brockman Adam , DuPont Michelle M. , Oller Haley , Gifford James , Lemelin Charles-Andre , Lim Soo Patrick , Perino Samantha , Moreau Benoît , Sharma Gitanjali , Shinde Rajesh , Sweryda-Krawiec Beata , Bilodeau Mark T. , Wooster Richard 
Published: October 2019

Abstract
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a 95% mortality rate with no improvement to treatment in decades, and new therapies are desperately needed. PEN-221 is a miniaturized peptide–drug conjugate (∼2 kDa) designed to target SCLC via a Somatostatin Receptor 2 (SSTR2)–targeting ligand and to overcome the high proliferation rate characteristic of this disease by using the potent cytotoxic payload, DM1. SSTR2 is an ideal target for a drug conjugate, as it is overexpressed in SCLC with limited normal tissue expression. In vitro, PEN-221 treatment of SSTR2-positive cells resulted in PEN-221 internalization and receptor-dependent inhibition of cellular proliferation. In vivo, PEN-221 exhibited rapid accumulation in SSTR2-positive SCLC xenograft tumors with quick clearance from plasma. Tumor accumulation was sustained, resulting in durable pharmacodynamic changes throughout the tumor, as evidenced by increases in the mitotic marker of G2–M arrest, phosphohistone H3, and increases in the apoptotic marker, cleaved caspase-3. PEN-221 treatment resulted in significant antitumor activity, including complete regressions in SSTR2-positive SCLC xenograft mouse models. Treatment was effective using a variety of dosing schedules and at doses below the MTD, suggesting flexibility of dosing schedule and potential for a large therapeutic window in the clinic. The unique attributes of the miniaturized drug conjugate allowed for deep tumor penetration and limited plasma exposure that may enable long-term dosing, resulting in durable tumor control. Collectively, these data suggest potential for antitumor activity of PEN-221 in patients with SSTR2-positive SCLC.
Essen Risk Score in Prediction of Myocardial Infarction After Transient Ischemic Attack or Ischemic Stroke Without Prior Coronary Artery Disease
Authors: Boulanger Marion , Li Linxin , Lyons Shane , Lovett Nicola G. , Kubiak Magdalena M. , Silver Louise , Touzé Emmanuel , Rothwell Peter M. ,   on behalf of the Oxford Vascular Study
Published: October 2019

Background and Purpose—
More intensive secondary prevention with newer drugs may be cost-effective in patients with coronary artery disease (CAD). Whether some subgroups of patients who had a transient ischemic attack (TIA) or ischemic stroke, but no prior CAD are at similar high risk of myocardial infarction as those with prior CAD remains unclear. We determined whether the Essen score identified a subset of TIA/stroke patients without known prior CAD who, nevertheless, had a high risk of myocardial infarction on current secondary prevention management.

Methods—
In a population-based cohort (Oxford Vascular Study) of consecutive TIA or ischemic stroke patients recruited from 2002 to 2014, 10-year actuarial risks of myocardial infarction and of recurrent ischemic stroke were determined by face-to-face follow-up in patients with and without prior CAD using Kaplan-Meier analyses. Predictive value of the Essen score was assessed with C statistic.

Results—

Of 2555 patients with TIA/stroke (13 070 patient-years of follow-up), 10-year risk of myocardial infarction in those without prior CAD (n=2017, 78.9%) ranged from 0.9% (95% CI, 0–1.9) at Essen score ≤1 to 29.8% (95% CI, 7.7–46.6) in those with a score ≥5 (C statistic =0.64 [95% CI, 0.57–0.71];
P
<0.001). The score tended to be less predictive (difference:
P
=0.0460) for the risk of recurrent ischemic stroke (C statistic =0.57 [95% CI, 0.54–0.60]). Compared with patients with prior CAD (n=538, 21.1%), an Essen risk score of ≥4 (n=294, 11.5%) in those without prior CAD identified a subgroup at similar high 10-year risks of myocardial infarction (17.2% [95% CI, 6.9–26.3] versus 16.9% [95% CI, 11.5–22.0]) and of recurrent stroke (40.4% [95% CI, 26.7–51.6] versus 32.4% [95% CI, 25.2–38.8]).

Conclusions—
The Essen score is a simple clinical score to risk-stratify patients with TIA/stroke without prior CAD and to identify subsets who may be at sufficiently high risk of myocardial infarction and recurrent stroke to justify more intensive treatment or inclusion in trials.
Exploring the Cost-Effectiveness of Mechanical Thrombectomy Beyond 6 Hours Following Advanced Imaging in the United Kingdom
Authors: Peultier Anne-Claire , Redekop William K. , Allen Michael , Peters Jaime , Eker Omer Faruk , Severens Johan L. 
Published: October 2019

Background and Purpose—
In the United Kingdom, mechanical thrombectomy (MT) for acute ischemic stroke patients assessed beyond 6 hours from symptom onset will be commissioned up to 12 hours provided that advanced imaging (AdvImg) demonstrates salvageable brain tissue. While the accuracy of AdvImg differs across technologies, evidence is limited regarding the proportion of patients who would benefit from late MT. We compared the cost-effectiveness of 2 care pathways: (1) MT within and beyond 6 hours based on AdvImg selection versus (2) MT only within 6 hours based on conventional imaging selection. The impact of varying AdvImg accuracy and prior probability for acute ischemic stroke patients to benefit from late MT was assessed.

Methods—
A decision tree and a Markov trace were developed. A hypothetical United Kingdom cohort of suspected stroke patients aged 71 years with first event was modeled. Costs, health outcomes, and probabilities were obtained from the literature. Outcomes included costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Probabilistic sensitivity analyses were performed. Various scenarios with prior probabilities of 10%, 20%, and 30%, respectively, for acute ischemic stroke patients to benefit from late MT, and with perfect accuracy, 80% sensitivity, and 70% specificity of AdvImg were studied.

Results—
Incremental cost-effectiveness ratios resulting from our deterministic analyses varied from $8199 (£6164) to $49 515 (£37 229) per QALY gained. AdvImg accuracy impacted the incremental cost-effectiveness ratio only when its specificity decreased. Over lifetime horizons, all scenarios including late MT improved QALYs and LYs. Depending on the scenario, the probabilistic sensitivity analyses showed probabilities varying between 46% and 93% for the late MT pathway to be cost-effective at a willingness to pay threshold of $39 900 (£30 000) per QALY.

Conclusions—
Late MT based on AdvImg selection may be good value for money. However, additional data regarding the implementation of AdvImg and prior probability to benefit from late MT are needed before its cost-effectiveness can be fully assessed.
Elucidating the Structural and Functional Correlates of Upper-Limb Poststroke Motor Impairment
Authors: Kemlin Claire , Moulton Eric , Lamy Jean-Charles , Houot Marion , Valabregue Romain , Leder Sara , Obadia Mickael A. , Meseguer Elena , Yger Marion , Brochard Vanessa , Corvol Jean-Christophe , Samson Yves , Rosso Charlotte 
Published: October 2019

Background and Purpose—
Many studies have attempted to bring to light the neural correlates of poststroke motor impairment, but few have used multimodal approach to explain it. The aim of this study was to elucidate neural structural and functional correlates of upper limb motor impairment by combining electrophysiological, anatomic, and functional neuroimaging data.

Methods—
Forty ischemic stroke patients (median [min–max] age: 63 [33–82] years, time poststroke: 3.5 [1.1–58] months) with unilateral upper limb weakness were included. The upper limb motor impairment was defined by a motor composite score. Simple linear analysis followed by multiple linear regression analysis were performed to identify which variables (corticospinal excitability, laterality indices within the primary motor cortex or corticospinal [CST], and corpus callosum tracts integrity) were the best explaining factors of upper limb motor impairment.

Results—

There was a significant correlation between the resting motor threshold ratio and CST damage (
r
= −0.50 [95% CI, −0.70 to −0.22];
P
<0.001) as well as the motor-evoked potentials amplitude (
r
= −0.73 [95% CI, −0.85 to −0.54];
P
<0.001). Only the resting motor threshold ratio was retained by the multiple regression model and explained half of the variance (49%;
P
<0.001) of the upper limb motor impairment after stroke.

Conclusions—
The implementation of quantitative neurophysiological measurements such as the resting motor threshold as a surrogate marker of impairment could be considered in neurorehabilitation trials.
Observed HIRS and MODIS High-Cloud Frequencies in the 2000s
Authors: Frey Richard A. , Menzel W. Paul 
Published: October 2019

AbstractThis paper compares the cloud parameter data records derived from High Resolution Infrared Radiation Sounder (HIRS) and Moderate Resolution Imaging Spectroradiometer (MODIS) measurements from the years 2003 through 2013. Cloud-top pressure (CTP) and effective emissivity (εf; cloud emissivity multiplied by cloud fraction) are derived using the 15-μm spectral bands in the CO2 absorption band and implementing the CO2-slicing technique; the approach is robust for high semitransparent clouds but weak for low clouds with little thermal contrast from clear-sky radiances. The high-cloud (HiCld; with CTP less than 440 hPa) seasonal cycles of HIRS and MODIS observations are found to be in sync, but the HIRS frequency of detection is about 10% higher than that of MODIS (which is attributed to a lower threshold for cloud detection in the HIRS CO2 bands). Differences are largest during nighttime and at the beginning of the time series (2003–06). Both show Northern Hemisphere (NH) and Southern Hemisphere (SH) seasonal HiClds are out of phase and both agree within 2% on NH–SH HiCld differences. During the summer, maximum HiCld frequency averages 5% more in the NH.
Characterizing the Energetics of Vortex-Scale and Sub-Vortex-Scale Asymmetries during Tropical Cyclone Rapid Intensity Changes
Authors: Marks Jr. Frank D. , Dubey S. , Shreevastava A. , Krishnamurti T. N. 
Published: October 2019

AbstractOur collective understanding of azimuthally asymmetric features within the coherent structure of a tropical cyclone (TC) continues to improve with the availability of more detailed observations and high-resolution model outputs. However, a precise understanding of how these asymmetries impact TC intensity changes is lacking. Prior attempts at investigating the asymmetric impacts follow a mean–eddy partitioning that condenses the effect of all the asymmetries into one term and fails to highlight the differences in the role of asymmetries at different scales. In this study, we present a novel energetics-based approach to analyze the asymmetric impacts at multiple length scales during periods of rapid intensity changes. Using model outputs of TCs under low and high shear, we compute the different energy pathways that enhance/suppress the growth of multiscale asymmetries in the wavenumber (WN) domain. We then compare and contrast the energetics of the mean-flow field (WN 0) with that of the persistent, coherent vortex-scale asymmetric structures (WNs 1 and 2) and the more local, transient, sub-vortex-scale asymmetries (WNs ≥ 3). We find in our case studies that the dominant mechanisms of growth/decay of the asymmetries are the baroclinic conversion from available potential to kinetic energy at individual scales of asymmetries and the transactions of kinetic energy between the asymmetries of various length scales, rather than the barotropic mean–eddy transactions as is typically assumed. Our case study analysis further shows that the growth/decay of asymmetries is largely independent of the mean. Certain aspects of eddy energetics can potentially serve as early-warning indicators of TC rapid intensity changes.
A Flexible Bayesian Approach to Bias Correction of Radar-Derived Precipitation Estimates over Complex Terrain: Model Design and Initial Verification
Authors: Chen Haonan , Cifelli Rob , Chandrasekar V. , Ma Yingzhao 
Published: October 2019

Abstract
This study develops a flexible Bayesian technique to quantify uncertainties associated with the operational Weather Surveillance Radar-1988 Doppler (WSR-88D) quantitative precipitation estimation (QPE) products over complex terrain. Radar-only rainfall estimates and rain gauge observations over the Russian River watershed in Northern California are utilized to demonstrate this new bias correction approach. Conventional mean field bias (MFB) and local bias (LB) correction methods are also implemented for comparison purposes. Results show that the proposed Bayesian technique outperforms the conventional MFB and LB correction approaches. The radar QPE performance is dramatically improved after the Bayesian-based bias correction: the root-mean-square error is reduced from 4.2 to 1.71 mm, the normalized mean absolute error is reduced from 64.5% to 24.2%, and the correlation with gauge measurements increases from 0.11 to 0.74. In addition, the terrain impact on radar QPE bias correction performance is investigated. After incorporating the terrain elevation information in the Bayesian framework, the QPE performance is further enhanced. Overall, the QPE performance scores after including the terrain information are improved about 10% relative to those only based on rainfall intensity values.
Atmospherically Forced Regional Ocean Simulations of the South China Sea: Scale Dependency of the Signal-to-Noise Ratio
Authors: Tang Shengquan , von Storch Hans , Chen Xueen 
Published: October 2019

AbstractWhen subjecting ocean models to atmospheric forcing, the models exhibits two types of variability—a response to the external forcing (hereafter referred to as signal) and inherently generated (internal, intrinsic, unprovoked, chaotic) variations (hereafter referred to as noise). Based on an ensemble of simulations with an identical atmospherically forced oceanic model that differ only in the initial conditions at different times, the signal-to-noise ratio of the atmospherically forced oceanic model is determined. In the large scales, the variability of the model output is mainly induced by the external forcing and the proportion of the internal variability is small, so the signal-to-noise ratio is large. For smaller scales, the influence of the external forcing weakens and the influence of the internal variability strengthens, so the signal-to-noise ratio becomes less and less. Thus, the external forcing is dominant for large scales, while most of the variability is internally generated for small scales.
On Baroclinic Instability over Continental Shelves: Testing the Utility of Eady-Type Models
Authors: Chen Shih-Nan , Chen Chiou-Jiu , Lerczak James A. 
Published: October 2019

AbstractThis study examines the utility of Eady-type theories as applied to understanding baroclinic instability in coastal flows where depth variations and bottom drag are important. The focus is on the effects of nongeostrophy, boundary dissipation, and bottom slope. The approach compares theoretically derived instability properties against numerical model calculations, for experiments designed to isolate the individual effects and justified to have Eady-like basic states. For the nongeostrophic effect, the theory of Stone (1966) is shown to give reasonable predictions for the most unstable growth rate and wavelength. It is also shown that the growing instability in a fully nonlinear model can be interpreted as boundary-trapped Rossby wave interactions—that is, wave phase locking and westward phase tilt allow waves to be mutually amplified. The analyses demonstrate that both the boundary dissipative and bottom slope effects can be represented by vertical velocities at the lower boundary of the unstable interior, via inducing Ekman pumping and slope-parallel flow, respectively, as proposed by the theories of Williams and Robinson (1974; referred to as the Eady–Ekman problem) and Blumsack and Gierasch (1972). The vertical velocities, characterized by a friction parameter and a slope ratio, modify the bottom wave and thus the scale selection. However, the theories have inherent quantitative limitations. Eady–Ekman neglects boundary layer responses that limit the increase of bottom stress, thereby overestimating the Ekman pumping and growth rate reduction at large drag. Blumsack and Gierasch’s (1972) model ignores slope-induced horizontal shear in the mean flow that tilts the eddies to favor converting energy back to the mean, thus having limited utility over steep slopes.
The Effects of Obstructive Sleep Apnea on Risk factors for Cardiovascular diseases
Authors: Jung Joo Hyun , Park Jung Woo , Kim Dong Hyun , Kim Seon Tae 
Published: October 2019

Introduction: Obstructive sleep apnea (OSA) is known to cause variety of cardiovascular diseases. Objective: The aim of this study was to examine the correlation between polysomnography (PSG) and risks factor for coronary heart disease in patients suspected to have OSA. Methods: A total of 108 consecutive adult habitual snorers underwent PSG. We assessed patients using the respiratory disturbance index (RDI), the Epworth sleepiness scale (ESS), body mass index (BMI), fasting serum total cholesterol, triglycerides (TGs), and C-reactive protein (CRP). Results: Mean RDI scores were 0.53, 10.6, 27.3, and 45.1 in the control group (n = 21), mild (n = 29), moderate (n = 31), and severe (n = 27), respectively. Partial correlation analysis showed that patients’ RDI score was significantly correlated with CRP after adjustment for BMI. Partial correlation analysis showed that the mean ESS score correlated significantly with the CRP level after adjustment for BMI. Partial correlation analysis showed that the mean least oxygen saturation was significantly correlated with CRP after adjustment for BMI Pearson’s correlation coefficients examining the relationship between BMI and total cholesterol; TG and CRP were found to be 0.531, 0.401, and 0.321. The correlation of CRP levels with disease severity as assessed by RDI, ESS, and least oxygen saturation was significant after adjustment for BMI. Conclusions: Patients with OSA have elevated serum levels of high-sensitivity-CRP, a marker for inflammation and an independent risk predictor for cardiovascular morbidity.