Toward Quantifying the Chemical Sensitivity of Nuclear Spin Surface Relaxivity in Mesoporous Media.

Low-field nuclear magnetic resonance (NMR) relaxation is a promising non-invasive technique for characterizing solid-liquid interactions within functional porous materials. However, the ability of the solid-liquid interface to enhance adsorbate relaxation rates, known as the surface relaxivity, in the case of different solvents and reagents involved in various chemical processes has yet to be evaluated in a quantitative manner. In this study, we systematically explore the surface relaxation characteristics of 10 liquid adsorbates (cyclohexane, acetone, water, and 7 alcohols, including ethylene glycol) confined within mesoporous silicas with pore sizes between 6 and 50 nm using low-field (12.7 MHz) two-dimensional 1H T1-T2 relaxation measurements. Functional-group-specific relaxation phenomena associated with the alkyl and hydroxyl groups of the confined alcohols are clearly distinguished; we report the dependence of both longitudinal (T1) and transverse (T2) relaxation rates of these 1H-bearing moieties on pore surface-to-volume ratio, facilitating the quantification and assignment of surface relaxivity values to specific functional groups within the same adsorbate molecule for the first time. We further demonstrate that alkyl group transverse surface relaxivities correlate strongly with the alkyl/hydroxyl ratio of the adsorbates assessed, providing evidence for a simple, quantitative relationship between surface relaxivity and interfacial chemistry. Overall, our observations highlight potential pitfalls in the application of NMR relaxation for the evaluation of pore size distributions using hydroxylated probe molecules, and provide motivation for the exploration of nuclear spin relaxation measurements as a route to adsorbate identity within functional porous materials.

NMR Surface Relaxivity in a Time-Dependent Porous System.

We demonstrate an unexpected decay-recovery behavior in the time-dependent ^{1}H NMR relaxation times of water confined within a hydrating porous material. Our observations are rationalized by considering the combined effects of decreasing material pore size and evolving interfacial chemistry, which facilitate a transition between surface-limited and diffusion-limited relaxation regimes. Such behavior necessitates the realization of temporally evolving surface relaxivity, highlighting potential caveats in the classical interpretation of NMR relaxation data obtained from complex porous systems.

Aqueous Solid Formation Kinetics in High-Pressure Methane at Trace Water Concentrations.

Natural gas containing trace amounts of water is frequently liquefied at conditions where aqueous solids are thermodynamically stable. However, no data are available to describe the kinetics of aqueous solid formation at these conditions. Here, we present experimental measurements of both solid formation kinetics and solid-fluid equilibrium for trace concentrations of (12 ± 0.7) ppm water in methane using a stirred, high-pressure apparatus and visual microscopy. Along isochoric pathways with cooling rates around 1 K·min-1, micron-scale aqueous solids were observed to form at subcoolings of (0.3-8.6) K, relative to an average equilibrium melting temperature of (253 ± 1.9) K at (8.9 ± 0.08) MPa; these data are consistent with predicted methane hydrate dissociation conditions within the uncertainty of both the experiment and model. The 36 measured formation events were used to construct a cumulative formation probability distribution, which was then fitted with a model from Classical Nucleation Theory, enabling the extraction of kinetic and thermodynamic nucleation parameters. While the resulting nucleation parameter values were comparable to those published for methane hydrate formation in bulk-water systems, the observed growth kinetics were distinctly different with only a small percentage of the water in the system converting into micron-scale solids over the experimental time scale. These results may help explain how cryogenic heat exchangers in liquefied natural gas facilities can operate for long periods without blockages forming despite being at very high subcoolings for aqueous solids.

A cost analysis of sorafenib for desmoid tumors.

INTRODUCTION: A recent randomized trial demonstrated that sorafenib improved progression free survival (PFS) in patients with desmoid tumors despite many patients experiencing stable disease or spontaneous regression without treatment. Utilizing these trial data, we performed a cost analysis of sorafenib efficacy through two years of treatment. METHODS: Current Medicare Part D rates for sorafenib were utilized (dose 400 mg/day, cost $309/day). Annual costs per progression and objective response were calculated. Radiologic progression and response were defined using RECIST criteria. Patients with disease progression were separately analyzed in two groups: both clinical and radiologic (CAR), and radiologic alone. RESULTS: 84 previously randomized patients were analyzed (placebo: 35, sorafenib: 49). At one year, sorafenib was associated with a 43% absolute risk reduction (ARR) of CAR progression and number-needed-to-treat (NNT) of 2.3 patients/year, costing $259,406. At two years, ARR was 48% and NNT of 2.1 patients/year, costing $473,697. When evaluating only patients with RECIST defined radiologic progression, sorafenib patients experienced ARR of 13.9% with NNT 7.2 and estimated costs of $812,052 at one year. Two-year ARR was 17.5% with NNT 5.7 and estimated costs $1,285,052. Sorafenib patients experienced improved RECIST partial response rates at 1 and 2 years of 14.7% and 14.3%, with NNT 6.8 and 6.9, and costs of $766,938 and $1,556,433; respectively. CONCLUSION: For the treatment of desmoid tumors, Sorafenib led to improved PFS, but at a significant cost per patient. Favorable RECIST outcomes were less likely and costlier. Patients should be informed of possible benefits of treatment versus potential financial burden.

Disparities in the prevalence of self-reported dysphagia and treatment among U.S. adults.

OBJECTIVE: To assess sociodemographic differences in the prevalence of self-reported dysphagia and treatment and to identify barriers in access to care. STUDY DESIGN: Cross-sectional analysis. SETTING: National healthcare survey database. METHODS: The 2012 National Health Interview Survey was used to analyze adults who reported a swallowing problem in the prior 12 months. Associations of sociodemographic variables with dysphagia prevalence and treatment as well as access to care were determined by multivariate logistic regression. RESULTS: Among 235 million adults in the United States, 9.4 ± 0.3 million (4.0 % ± 0.1 %) adults (mean age 52.1 ± 0.6 years; 60.2 % female) reported swallowing problems, only 19.2 % ± 2.0 % of whom reported receiving treatment or therapy for their swallowing problem. In a multivariate model controlling for sociodemographic factors, female gender, older age, lower income level, public insurance status and unemployment were independently associated with increased odds of reporting dysphagia, while also associated with decreased odds of receiving treatment. Conversely, Black, Hispanic and other racial/ethnic minorities were less likely to report swallowing problems, but among those who did report dysphagia, non-white adults were more likely to receive treatment. Barriers leading to delayed care for women, low-income adults and adults with public or no health insurance included cost, not being able to get an appointment soon enough, limited office hours, inability to get through to an office by phone, lack of transportation, and long office wait times. CONCLUSION: Sociodemographic groups at higher risk for dysphagia are less likely to receive treatment. Targeted interventions are needed to address barriers to care. LEVEL OF EVIDENCE: IV.

Performance on stochastic figure-ground perception varies with individual differences in speech-in-noise recognition and working memory capacity.

Speech recognition in noisy environments can be challenging and requires listeners to accurately segregate a target speaker from irrelevant background noise. Stochastic figure-ground (SFG) tasks in which temporally coherent inharmonic pure-tones must be identified from a background have been used to probe the non-linguistic auditory stream segregation processes important for speech-in-noise processing. However, little is known about the relationship between performance on SFG tasks and speech-in-noise tasks nor the individual differences that may modulate such relationships. In this study, 37 younger normal-hearing adults performed an SFG task with target figure chords consisting of four, six, eight, or ten temporally coherent tones amongst a background of randomly varying tones. Stimuli were designed to be spectrally and temporally flat. An increased number of temporally coherent tones resulted in higher accuracy and faster reaction times (RTs). For ten target tones, faster RTs were associated with better scores on the Quick Speech-in-Noise task. Individual differences in working memory capacity and self-reported musicianship further modulated these relationships. Overall, results demonstrate that the SFG task could serve as an assessment of auditory stream segregation accuracy and RT that is sensitive to individual differences in cognitive and auditory abilities, even among younger normal-hearing adults.

Social media emotions annotation guide (SMEmo): Development and initial validity.

The proper measurement of emotion is vital to understanding the relationship between emotional expression in social media and other factors, such as online information sharing. This work develops a standardized annotation scheme for quantifying emotions in social media using recent emotion theory and research. Human annotators assessed both social media posts and their own reactions to the posts' content on scales of 0 to 100 for each of 20 (Study 1) and 23 (Study 2) emotions. For Study 1, we analyzed English-language posts from Twitter (N = 244) and YouTube (N = 50). Associations between emotion ratings and text-based measures (LIWC, VADER, EmoLex, NRC-EIL, Emotionality) demonstrated convergent and discriminant validity. In Study 2, we tested an expanded version of the scheme in-country, in-language, on Polish (N = 3648) and Lithuanian (N = 1934) multimedia Facebook posts. While the correlations were lower than with English, patterns of convergent and discriminant validity with EmoLex and NRC-EIL still held. Coder reliability was strong across samples, with intraclass correlations of .80 or higher for 10 different emotions in Study 1 and 16 different emotions in Study 2. This research improves the measurement of emotions in social media to include more dimensions, multimedia, and context compared to prior schemes.

Low-Field NMR Relaxation Analysis of High-Pressure Ethane Adsorption in Mesoporous Silicas.

Understanding the behaviour of short-chain hydrocarbons confined to porous solids informs the targeted extraction of natural resources from geological features, and underpins rational developments in separation, storage and catalytic conversion processes. Herein, we report the application of low-field (12.7 MHz) 1 H nuclear magnetic resonance (NMR) relaxation measurements to characterise ethane dynamics within mesoporous silica materials exhibiting mean pore diameters between 6 and 50 nm. Our measurements provide NMR-based adsorption isotherms within the range 25-50 bar and at ambient temperature, incorporating the ethane condensation point (40.7 bar at our experimental temperature of 23.6 °C). The quantitative nature of the acquired data is validated via a direct comparison of NMR-derived excess adsorption capacities with ex situ gravimetric ethane adsorption measurements, which are demonstrated to agree to within 0.2 mmol g-1 of the observed ethane capacity. NMR T2 relaxation time distributions are further demonstrated as a means to decouple interparticle and mesopore dominated adsorption phenomena, with unexpectedly rapid relaxation rates associated with interparticle ethane gas confirmed via a direct comparison with NMR self-diffusion analysis.

Episodes of high recruitment buffer against climate-driven mass mortality events in a North Pacific seabird population.

Longitudinal studies of marked animals provide an opportunity to assess the relative contributions of survival and reproductive output to population dynamics and change. Cassin's auklets are a long-lived seabird that maximizes annual reproductive effort in resource-rich years through a behaviour called double brooding, the initiation of a second breeding attempt following the success of the first during the same season. Our objective was to explore whether double brooding influenced population change by contributing a greater number of future recruits. We fit temporal symmetry models to 32 years of mark-recapture data of Cassin's auklets to infer the mechanisms underlying the observed variability in per capita recruitment rates. We found that periodic peaks in recruitment were explained by an increase in available nest sites, the proportion of the population double brooding 4 years prior, and spring upwelling conditions. Estimates of population change suggests a relatively stable population throughout the time series, attributable to a 'floating' demographic class of sexually mature individuals excluded from breeding by competition which quickly fill vacant sites following periods of low adult survival. Our results highlight the importance of recruitment in maintaining the population of a long-lived seabird periodically impacted by adverse environmental conditions.

Discovery of 4-(3-aminopyrrolidinyl)-3-aryl-5-(benzimidazol-2-yl)-pyridines as potent and selective SST5 agonists for the treatment of congenital hyperinsulinism.

SST5 receptor activation potently inhibits insulin secretion from pancreatic ß-cells, and an orally available nonpeptide selective SST5 agonist may be used to effectively manage the blood glucose levels of congenital HI patients to avoid severe hypoglycemia. Our medicinal chemistry efforts have led to the discovery of 4-(3-aminopyrrolidinyl)-3-aryl-5-(benzimidazol-2-yl)-pyridine analogs as potent SST5 agonists. This class of molecules exhibits excellent human SST5 potency and selectivity against SST1, SST2, SST3 and SST4 receptors. Leading compound 3-{4-[(3S)-3-aminopyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-3-yl-5-fluorobenzonitrile (28, CRN02481) showed limited off-target activity and good pharmacokinetic profiles in both male Sprague Dawley rats and Beagle dogs to advance into further preclinical evaluations.

Oceanographic drivers of winter habitat use in Cassin's Auklets.

Reduced prey abundance and severe weather can lead to a greater risk of mortality for seabirds during the non-breeding winter months. Resource patterns in some regions are shifting and becoming more variable in relation to past conditions, potentially further impacting survival and carryover to the breeding season. As animal tracking technologies and methods to analyze movement data have advanced, it has become increasingly feasible to draw fine-scale inference about how environmental variation affects foraging behavior and habitat use of seabirds during this critical period. Here, we used archival light-sensing tags to evaluate how interannual variation in oceanography affected the winter distribution of Cassin's Auklets from Southeast Farallon Island, California. Thirty-five out of 93 geolocators deployed from 2015 to 2017 were recovered and successfully recorded light-level data, from which geographic positions were estimated. Step-selection functions were applied to identify environmental covariates that best explained winter movement decisions and habitat use, revealing Cassin's Auklets dispersed farther from the colony during a winter with warm SST anomalies, but remained more centralized near the breeding colony during two average winters. Movement patterns were driven by avoidance of areas with higher sea surface temperatures and possible limits of dispersal from the breeding colony, and selection for areas with well-defined mesoscale fronts and cooler surface waters. Through multiple years of tagging and the application of step-selection functions, a robust and widely applied approach for analyzing animal movement in terrestrial species, we show how interannual differences in the movement patterns of a small seabird are driven by oceanographic variability across years. Understanding the winter habitat use of seabirds can help inform changes in population structure and measures of reproductive success, aiding managers in determining potential causes of breeding failures.

Low-field NMR relaxation-exchange measurements for the study of gas admission in microporous solids.

Understanding the uptake and storage of gases by microporous materials is important for our future energy security. As such, we demonstrate here the application of two-dimensional NMR relaxation experiments for probing the admission and corresponding exchange dynamics of methane within microporous zeolites. Specifically, we report low-field (12.7 MHz) 1H NMR relaxation-exchange correlation measurements of methane within commercial LTA zeolites (3A and 4A) at 25 and 35 bar and ambient temperature. Our results demonstrate the clear identification of bulk-pore and pore-pore exchange processes within zeolite 4A, facilitating the calculation and comparison of effective exchange rate dynamics across varying diffusion length scales and gas pressures. Additional data acquired for zeolite 3A reveals the sensitivity of NMR relaxation phenomena to size-exclusive gas admission phenomena, illustrating the potential of benchtop NMR protocols for material screening applications.

Hydrate nucleation and growth on water droplets acoustically-levitated in high-pressure natural gas.

Hydrate formation was studied using water droplets acoustically levitated in high-pressure natural gas. Despite the absence of solid interfaces, the droplets' area-normalised nucleation rate was about four times faster than in steel autoclave measurements with interfacial areas roughly 200 times larger. Multiple stages of stochastic, template-free hydrate growth were observed.

Increased reproductive investment associated with greater survival and longevity in Cassin's auklets.

Individuals increase lifetime reproductive output through a trade-off between investment in future survival and immediate reproductive success. This pattern may be obscured in certain higher quality individuals that possess greater reproductive potential. The Cassin's auklet (Ptychoramphus aleuticus) is a long-lived species where some individuals exhibit greater reproductive ability through a behaviour called double brooding. Here, we analyse 32 years of breeding histories from marked known-age auklets to test whether double brooding increases lifetime fitness despite the increased mortality and reduced lifespan higher reproductive effort would be expected to incur. Multistate mark-recapture modelling revealed that double brooding was strongly positively associated with higher annual survival and longevity. The mean (95% confidence interval) apparent survival was 0.69 (0.21, 0.91) for individuals that executed a single brood and 0.96 (0.84, 0.99) for those that double-brooded. Generalized linear mixed models indicated individuals that attempted multiple double broods over their lifetime were able to produce on average seven times as many chicks and live nearly 6 years longer than birds that never attempted a double brood. We found that high-quality individuals exhibited both increased reproductive effort and longevity, where heterogeneity in individual quality masked expected life-history trade-offs.

Gas Hydrate Formation Probability Distributions: The Effect of Shear and Comparisons with Nucleation Theory.

Gas hydrate formation is a stochastic phenomenon of considerable significance for any risk-based approach to flow assurance in the oil and gas industry. In principle, well-established results from nucleation theory offer the prospect of predictive models for hydrate formation probability in industrial production systems. In practice, however, heuristics are relied on when estimating formation risk for a given flowline subcooling or when quantifying kinetic hydrate inhibitor (KHI) performance. Here, we present statistically significant measurements of formation probability distributions for natural gas hydrate systems under shear, which are quantitatively compared with theoretical predictions. Distributions with over 100 points were generated using low-mass, Peltier-cooled pressure cells, cycled in temperature between 40 and -5 °C at up to 2 K·min-1 and analyzed with robust algorithms that automatically identify hydrate formation and initial growth rates from dynamic pressure data. The application of shear had a significant influence on the measured distributions: at 700 rpm mass-transfer limitations were minimal, as demonstrated by the kinetic growth rates observed. The formation probability distributions measured at this shear rate had mean subcoolings consistent with theoretical predictions and steel-hydrate-water contact angles of 14-26°. However, the experimental distributions were substantially wider than predicted, suggesting that phenomena acting on macroscopic length scales are responsible for much of the observed stochastic formation. Performance tests of a KHI provided new insights into how such chemicals can reduce the risk of hydrate blockage in flowlines. Our data demonstrate that the KHI not only reduces the probability of formation (by both shifting and sharpening the distribution) but also reduces hydrate growth rates by a factor of 2.

New York City flavoured tobacco product sales ban evaluation.

INTRODUCTION: The availability of flavoured tobacco products is associated with increased initiation and youth smoking. New York City prohibited all sales of flavoured cigars, cigarillos, little cigars, chew, snuff, snus, tobacco, pipe tobacco, roll-your-own tobacco, and dissolvables, excluding menthol, in October 2009; enforcement began in November 2010. This paper describes the sales ban evaluation. METHODS: Data on retail tobacco sales of cigars, smokeless and other tobacco products such as pipe tobacco and roll-your-own, were analysed using interrupted time series methods, estimating changes in flavoured and non-flavoured tobacco product inflation-adjusted dollar sales overall, and by product type. Changes in ever use of flavoured tobacco products, any tobacco product use, and smoking prevalence among adolescents were estimated using multivariable logistic regression. RESULTS: Sales of flavoured tobacco products declined overall (87%; p<0.001), and for flavoured cigars (86%; p<0.001) and flavoured pipe and roll-your-own (91%; p<0.001) following ban enforcement, while non-flavoured sales increased for cigars (5%; p=0.003) and pipe and roll-your-own (4%, p=0.030). In adjusted models, teens in 2013 had 37% lower odds of ever trying flavoured tobacco products (p<0.001), 28% lower odds of using any type of tobacco product (p=0.025), and a non-significant change in current smoking prevalence (p=0.114) compared with teens in 2010. CONCLUSIONS: Flavoured tobacco product sales and odds of ever using flavoured tobacco products or using any tobacco products among teens declined significantly after ban enforcement began. Collectively these findings demonstrate significant evidence that the flavoured tobacco products sales ban was successful in New York City, and could succeed elsewhere.

PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression.

Tissue factor (TF) (CD142) is a 47 kDa transmembrane cell surface glycoprotein that triggers the extrinsic coagulation cascade and links thrombosis with inflammation. Although macrophage TF expression is known to be regulated at the RNA level, very little is known about the mechanisms involved. Poly(adenosine 5'-diphosphate [ADP]-ribose)-polymerase (PARP)-14 belongs to a family of intracellular proteins that generate ADP-ribose posttranslational adducts. Functional screening of PARP-14-deficient macrophages mice revealed that PARP-14 deficiency leads to increased TF expression and functional activity in macrophages after challenge with bacterial lipopolysaccharide. This was related to an increase in TF messenger RNA (mRNA) stability. Ribonucleoprotein complex immunoprecipitation and biotinylated RNA pull-down assays demonstrated that PARP-14 forms a complex with the mRNA-destabilizing protein tristetraprolin (TTP) and a conserved adenylate-uridylate-rich element in the TF mRNA 3' untranslated region. TF mRNA regulation by PARP-14 was selective, as tumor necrosis factor (TNF)α mRNA, which is also regulated by TTP, was not altered in PARP-14 deficient macrophages. Consistent with the in vitro data, TF expression and TF activity, but not TNFα expression, were increased in Parp14(-/-) mice in vivo. Our study provides a novel mechanism for the posttranscriptional regulation of TF expression, indicating that this is selectively regulated by PARP-14.

Oral administration of SR-110, a peroxynitrite decomposing catalyst, enhances glucose homeostasis, insulin signaling, and islet architecture in B6D2F1 mice fed a high fat diet.

Peroxynitrite has been implicated in type 2 diabetes and diabetic complications. As a follow-up study to our previous work on SR-135 (Arch Biochem Biophys 577-578: 49-59, 2015), we provide evidence that this series of compounds are effective when administered orally, and their mechanisms of actions extend to the peripheral tissues. A more soluble analogue of SR-135, SR-110 (from a new class of Mn(III) bis(hydroxyphenyl)-dipyrromethene complexes) was orally administered for 2 weeks to B6D2F1 mice fed a high fat-diet (HFD). Mice fed a HFD for 4 months gained significantly higher body weights compared to lean diet-fed mice (52 ± 1.5 g vs 34 ± 1.3 g). SR-110 (10 mg/kg daily) treatment significantly reduced fasting blood glucose and insulin levels, and enhanced glucose tolerance as compared to HFD control or vehicle (peanut butter) group. SR-110 treatment enhanced insulin signaling in the peripheral organs, liver, heart, and skeletal muscle, and reduced lipid accumulation in the liver. Furthermore, SR-110 increased insulin content, restored islet architecture, decreased islet size, and reduced tyrosine nitration. These results suggest that a peroxynitrite decomposing catalyst is effective in improving glucose homeostasis and restoring islet morphology and ß-cell insulin content under nutrient overload.

Raman Spectroscopic Studies of Clathrate Hydrate Formation in the Presence of Hydrophobized Particles.

In the present work, Raman spectroscopy was used to study the structure of water molecules in the vicinity of glass particles with different hydrophobicity, immersed in water and in tetrahydrofuran and cyclopentane hydrates. The glass particle surfaces were clean (hydrophilic), coated with N,N-dimethyl-N-octadecyl-3-aminopropyl trimethoxysilyl chloride (partially hydrophobic), or coated with octadecyltrichlorosilane (hydrophobic). The Raman spectra indicate that, prior to nucleation, water molecules in the vicinity of hydrophobic surfaces are more ice-like ordered than those in the bulk liquid or near either hydrophilic or partially hydrophobic surfaces. Furthermore, the degree of hydrogen-bond ordering of water observed prior to hydrate nucleation, as measured by the ratio of the inter- and intramolecular Raman OH bands, was found to have an inverse relationship with the mean induction time for hydrate formation. Following hydration formation, no significant difference in the water molecule structure was observed in the hydrate phase based on their Raman OH bands, irrespective of surface hydrophobicity. These observations made with Raman spectroscopy provide the foundations for a quantitative link between hydrate nucleation promotion and water-ordering near solid surfaces, which could enable direct comparisons with results from corresponding molecular dynamics simulations.

Predictors of Posterior Glottic Stenosis: A Multi-Institutional Case-Control Study.

OBJECTIVE: To assess intrinsic and extrinsic risk factors in the development of posterior glottic stenosis (PGS) in intubated patients. METHODS: Patients diagnosed with PGS between September 2012 and May 2014 at 3 tertiary care university hospitals were included. Patient demographics, comorbidities, duration of intubation, endotracheal tube (ETT) size, and indication for intubation were recorded. Patients with PGS were compared to control patients represented by patients intubated in intensive care units (ICU). RESULTS: Thirty-six PGS patients were identified. After exclusion, 28 PGS patients (14 male, 14 female) and 112 (65 male, 47 female) controls were studied. Multivariate analysis demonstrated ischemia (P < .05), diabetes (P < .01), and length of intubation (P < .01) were significant risk factors for the development of PGS. Fourteen of 14 (100%) males were intubated with a size 8 or larger ETT compared to 47 of 65 (72.3%) male controls (P < .05). Posterior glottic stenosis (P < .01), length of intubation (P < .001), and obstructive sleep apnea (P < .05) were significant risk factors for tracheostomy. CONCLUSION: Duration of intubation, ischemia, diabetes mellitus, and large ETT size (8 or greater) in males were significant risk factors for the development of PGS. Reducing the use of size 8 ETTs and earlier planned tracheostomy in high-risk patients may reduce the incidence of PGS and improve ICU safety.