Predictors of attrition in a randomized controlled trial of an electronic nicotine delivery system among people interested in cigarette smoking reduction.

BACKGROUND: Mitigating attrition is a key component to reduce selection bias in longitudinal randomized controlled trials (RCTs). Few studies of electronic nicotine delivery systems (ENDS) allow for the examination of long-term retention. This analysis explores the relationship between attrition, baseline measures, and condition assigned for a RCT involving ENDS differing in nicotine delivery over a 24-week intervention period. METHODS: Participants (N = 520) who smoked ≥10 cigarettes per day [CPD] for ≥1 year and reported interest in reducing but not quitting were randomized to 1 of 4 conditions: an ENDS containing 0, 8, or 36 mg/ml liquid nicotine (administered double-blind) or a cigarette-shaped plastic tube. Cox proportional hazards regression models were fit to examine attrition over time and predictors of attrition including baseline characteristics and condition. A stepwise approach was used to determine the final model; alpha was set at 0.05. RESULTS: Attrition did not differ significantly by condition (223/520), and most (69%) were lost-to-follow-up. Only age, education level, and household income were significantly predictive of attrition. For every additional year of age, attrition risk fell by 3%. Holding a bachelor's degree or higher was associated with reduced attrition risk. Those with the lowest income (<$10 K) were more likely to be withdrawn compared to those earning $10 K-39 K, and those with the highest income ($100 K+) were more likely to be withdrawn compared with the latter bracket and those earning $70-99 K. CONCLUSION: ENDS nicotine content did not drive differential attrition in this trial, and targeted retention efforts is needed for specific subgroups. Trial Registration #: NCT02342795.

Hippocampal sclerosis and temporal lobe epilepsy following febrile status epilepticus: The FEBSTAT study.

OBJECTIVE: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. METHODS: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. RESULTS: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. SIGNIFICANCE: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.

A monotone single index model for missing-at-random longitudinal proportion data.

Beta distributions are commonly used to model proportion valued response variables, often encountered in longitudinal studies. In this article, we develop semi-parametric Beta regression models for proportion valued responses, where the aggregate covariate effect is summarized and flexibly modeled, using a interpretable monotone time-varying single index transform of a linear combination of the potential covariates. We utilize the potential of single index models, which are effective dimension reduction tools and accommodate link function misspecification in generalized linear mixed models. Our Bayesian methodology incorporates the missing-at-random feature of the proportion response and utilize Hamiltonian Monte Carlo sampling to conduct inference. We explore finite-sample frequentist properties of our estimates and assess the robustness via detailed simulation studies. Finally, we illustrate our methodology via application to a motivating longitudinal dataset on obesity research recording proportion body fat.

Spontaneous Appearance of Triiodide Covering the Topmost Layer of the Iodide Solution Interface Without Photo-Oxidation.

Ions containing iodine atoms at the vapor-aqueous solution interfaces critically affect aerosol growth and atmospheric chemistry due to their complex chemical nature and multivalency. While the surface propensity of iodide ions has been intensely discussed in the context of the Hofmeister series, the stability of various ions containing iodine atoms at the vapor-water interface has been debated. Here, we combine surface-specific sum-frequency generation (SFG) vibrational spectroscopy with ab initio molecular dynamics simulations to examine the extent to which iodide ions cover the aqueous surface. The SFG probe of the free O-D stretch mode of heavy water indicates that the free O-D group density decreases drastically at the interface when the bulk NaI concentration exceeds ∼2 M. The decrease in the free O-D group density is attributed to the spontaneous appearance of triiodide that covers the topmost interface rather than to the surface adsorption of iodide. This finding demonstrates that iodide is not surface-active, yet the highly surface-active triiodide is generated spontaneously at the water-air interface, even under dark and oxygen-free conditions. Our study provides an important first step toward clarifying iodine chemistry and pathways for aerosol formation.

Ultrafast Surface-Specific Spectroscopy of Water at a Photoexcited TiO2 Model Water-Splitting Photocatalyst.

A critical step in photocatalytic water dissociation is the hole-mediated oxidation reaction. Molecular-level insights into the mechanism of this complex reaction under realistic conditions with high temporal resolution are highly desirable. Here, we use femtosecond time-resolved, surface-specific vibrational sum frequency generation spectroscopy to study the photo-induced reaction directly at the interface of the photocatalyst TiO2 in contact with liquid water at room temperature. Thanks to the inherent surface specificity of the spectroscopic method, we can follow the reaction of solely the interfacial water molecules directly at the interface at timescales on which the reaction takes place. Following the generation of holes at the surface immediately after photoexcitation of the catalyst with UV light, water dissociation occurs on a sub-20 ps timescale. The reaction mechanism is similar at pH 3 and 11. In both cases, we observe the conversion of H2 O into Ti-OH groups and the deprotonation of pre-existing Ti-OH groups. This study provides unique experimental insights into the early steps of the photo-induced dissociation processes at the photocatalyst-water interface, relevant to the design of improved photocatalysts.

Evidence-based guideline for the prevention and management of perioperative infection.

BACKGROUND: We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. METHODS: We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. RESULTS: There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. CONCLUSIONS: This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.

A review of whole-process control of industrial volatile organic compounds in China.

Volatile organic compounds (VOCs) play an important role in the formation of ground-level ozone and secondary organic aerosol (SOA), and they have been key issues in current air pollution prevention and control in China. Considerable attention has been paid to industrial activities due to their large and relatively complex VOCs emissions. The present research aims to provide a comprehensive review on whole-process control of industrial VOCs, which mainly includes source reduction, collection enhancement and end-pipe treatments. Lower VOCs materials including water-borne ones are the keys to source substitution in industries related to coating and solvent usage, leak detection and repair (LDAR) should be regarded as an efficient means of source reduction in refining, petrochemical and other chemical industries. Several types of VOCs collection methods such as gas-collecting hoods, airtight partitions and others are discussed, and airtight collection at negative pressure yields the best collection efficiency. Current end-pipe treatments like UV oxidation, low-temperature plasma, activated carbon adsorption, combustion, biodegradation, and adsorption-combustion are discussed in detail. Finally, several recommendations are made for future advanced treatment and policy development in industrial VOCs emission control.

Bulklike Vibrational Coupling of Surface Water Revealed by Sum-Frequency Generation Spectroscopy.

Vibrational coupling between interfacial water molecules is important for energy dissipation after on-water chemistry, yet intensely debated. Here, we quantify the interfacial vibrational coupling strength through the linewidth of surface-specific vibrational spectra of the water's O─H (O─D) stretch region for neat H_{2}O/D_{2}O and their isotopic mixtures. The local-field-effect-corrected experimental SFG spectra reveal that the vibrational coupling between hydrogen-bonded interfacial water O─H groups is comparable to that in bulk water, despite the effective density reduction at the interface.

Polarization-Dependent Heterodyne-Detected Sum-Frequency Generation Spectroscopy as a Tool to Explore Surface Molecular Orientation and Ångström-Scale Depth Profiling.

Sum-frequency generation (SFG) spectroscopy provides a unique optical probe for interfacial molecules with interface-specificity and molecular specificity. SFG measurements can be further carried out at different polarization combinations, but the target of the polarization-dependent SFG is conventionally limited to investigating the molecular orientation. Here, we explore the possibility of polarization-dependent SFG (PD-SFG) measurements with heterodyne detection (HD-PD-SFG). We stress that HD-PD-SFG enables accurate determination of the peak amplitude, a key factor of the PD-SFG data. Subsequently, we outline that HD-PD-SFG can be used not only for estimating the molecular orientation but also for investigating the interfacial dielectric profile and studying the depth profile of molecules. We further illustrate the variety of combined simulation and PD-SFG studies.

Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid ß (16-22) Peptides at the Air-Water Interface.

Assembly by amyloid-beta (Aß) peptides is vital for various neurodegenerative diseases. The process can be accelerated by hydrophobic interfaces such as the cell membrane interface and the air-water interface. Elucidating the assembly mechanism for Aß peptides at hydrophobic interface requires knowledge of the microscopic structure of interfacial peptides. Here we combine scanning force microscopy, sum-frequency generation spectroscopy, and metadynamics simulations to probe the structure of the central fragment of Aß peptides at the air-water interface. We find that the structure of interfacial peptides depends on pH: at neutral pH, the peptides adopt a less folded, bending motif by forming intra-hydrogen bonds; at acidic pH, the peptides refold into extended ß-strand fibril conformation, which further promotes their macroscopic assembly. The conformational transition of interfacial peptides is driven by the reduced hydrogen bonds, both with water and within peptides, resulting from the protonation of acidic glutamic acid side chains.

Accurate molecular orientation at interfaces determined by multimode polarization-dependent heterodyne-detected sum-frequency generation spectroscopy via multidimensional orientational distribution function.

Many essential processes occur at soft interfaces, from chemical reactions on aqueous aerosols in the atmosphere to biochemical recognition and binding at the surface of cell membranes. The spatial arrangement of molecules specifically at these interfaces is crucial for many of such processes. The accurate determination of the interfacial molecular orientation has been challenging due to the low number of molecules at interfaces and the ambiguity of their orientational distribution. Here, we combine phase- and polarization-resolved sum-frequency generation (SFG) spectroscopy to obtain the molecular orientation at the interface. We extend an exponentially decaying orientational distribution to multiple dimensions, which, in conjunction with multiple SFG datasets obtained from the different vibrational modes, allows us to determine the molecular orientation. We apply this new approach to formic acid molecules at the air-water interface. The inferred orientation of formic acid agrees very well with ab initio molecular dynamics data. The phase-resolved SFG multimode analysis scheme using the multidimensional orientational distribution thus provides a universal approach for obtaining the interfacial molecular orientation.

The impact of antimicrobial stewardship program designed to shorten antibiotics use on the incidence of resistant bacterial infections and mortality.

Reassessing the continuing need for and choice of antibiotics by using an antibiotic "time out'' program may reduce unnecessary treatment. This study aimed to explore the effect of an antibiotic stewardship program (ASP) on the antibiotics consumption, incidence of resistant bacterial infections and overall hospital mortality in a tertiary medical center during the study period 2012-2014. An ASP composed of multidisciplinary strategies including pre-prescription approval and post-approval feedback and audit, and a major "time out'' intervention (shorten the default antibiotic prescription duration) usage was introduced in year 2013. Consumption of antibiotics was quantified by calculating defined daily doses (DDDs). Interrupted time series (ITS) analysis was used to explore the changes of antibiotics consumption before and after intervention, accounting for temporal trends that may be unrelated to intervention. Our results showed that following the intervention, DDDs showed a decreased trend in overall (in particular the major consumed penicillins and cephalosporins), in both intensive care unit (ICU) and non-ICU, and in non-restrictive versus restrictive antibiotics. Importantly, ITS analysis showed a significantly slope change since intervention (slope change p value 0.007), whereas the incidence of carbapenem-resistant and vancomycin-resistant pathogens did not change significantly. Moreover, annual overall mortality rates were 3.0%, 3.1% and 3.1% from 2012 to 2014, respectively. This study indicates that implementing a multi-disciplinary strategy to shorten the default duration of antibiotic prescription can be an effective manner to reduce antibiotic consumption while not compromising resistant infection incidence or mortality rates.

Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial.

INTRODUCTION: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute. METHODS: This four-arm parallel-group, randomized, placebo-controlled trial took place at two academic medical centers in the United States (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N = 520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8, or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization. RESULTS: At 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI = 1.9-104.9] and 3.5 [95% CI = 1.2-10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130). CONCLUSIONS: When smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute. IMPLICATIONS: The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.

Childhood waist growth curves and adult diabetes.

Our primary objectives are to empirically identify distinct childhood groups based on trajectories of waist circumference (WC) and waist circumference index measurements, and then to estimate associations between these groups and adult diabetes incidence, as well as other outcomes, including blood pressure, body size, body composition, and hemoglobin levels. Childhood WC and height measurements as well as various adult measurements are taken from participants in the Fels Longitudinal Study. Childhood groups are identified using group-based trajectory modeling. Associations between the resulting group probabilities and adult outcomes are examined using mixed models. Our results show that distinct childhood groups are identifiable for both waist size measurements, with growth curves exhibited by these groups becoming distinguishably separate at around 4 years of age. Higher probabilities for groups exhibiting the larger waist size for either measurement were estimated to have higher risks of developing diabetes in adulthood. Associations were also observed between group probabilities and systolic blood pressure, diastolic blood pressure, and various anthropomorphic measurements, with most associations consistently occurring in early adulthood. These findings expand upon the existing literature, showing that childhood trends in waist size, distinguishable at ages as early as 4 years, are associated with adult Type-2 diabetes.

The Effect of Letrozole Combined with Dydrogesterone for Endometriosis in China: A Meta-Analysis.

PURPOSE: To discuss the effects of dydrogesterone combined with letrozole on the effectiveness, sex hormone levels, and serological indicators in patients with endometriosis. This study is registered with PROSPERO (CRD42020213172). METHODS: We searched relevant randomized controlled trials (RCTs) through PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP Database. The standardized mean differences (SMDs), the mean differences (MDs), or odds ratios (ORs) with their 95% confidence intervals (95% CIs) were computed to be outcome indicators, including total effectiveness, Vascular Endothelial Growth Factor (VEGF) level, Carbohydrate Antigen 125 (CA125) level, Follicle-Stimulating Hormone (FSH) level, Luteinizing Hormone (LH) level, estrogen (E2) level, progesterone (P) level, interleukin-6 (IL-6) level, and tumor necrosis factor-a (TNF-a) level. RESULTS: A total of 19 RCTs involving 1,591 patients were included in this study. Our results showed that letrozole combined with dydrogesterone can significantly reduce the levels of VEGF (SMD -2.23, 95% CI -2.39 to -2.07; p < 0.00001), CA125 (MD -10.53, 95% CI -11.19 to -9.88; p < 0.00001), E2 (SMD -1.64, 95% CI -1.81 to -1.47; p < 0.00001), P (MD -5.11, 95% CI -6.26 to -3.96; p < 0.00001), IL-6 (MD -4.41, 95% CI -5.16 to -3.67; p < 0.00001), and TNF-a (MD -5.67, 95% CI -6.34 to -5.00; p < 0.00001) in patients with endometriosis compared with the control group. In addition, the results indicated that total effectiveness was significantly higher in the experiment group (OR 6.21, 95% CI 4.17 to 9.24; p < 0.00001) compared to the control. However, there was no significant difference between FSH and LH levels in both groups (p > 0.05). CONCLUSION: This combination therapy can effectively decrease the levels of VEGF, CA125, E2, P, IL-6, and TNF-a and increase the total effectiveness when comparing with the control group.

Interfacial Water Structure of Binary Liquid Mixtures Reflects Nonideal Behavior.

The evaporation of molecules from water-organic solute binary mixtures is key for both atmospheric and industrial processes such as aerosol formation and distillation. Deviations from ideal evaporation energetics can be assigned to intermolecular interactions in solution, yet evaporation occurs from the interface, and the poorly understood interfacial, rather than the bulk, structure of binary mixtures affects evaporation kinetics. Here we determine the interfacial structure of nonideal binary mixtures of water with methanol, ethanol, and formic acid, by combining surface-specific vibrational spectroscopy with molecular dynamics simulations. We find that the free, dangling OH groups at the interfaces of these differently behaving nonideal mixtures are essentially indistinguishable. In contrast, the ordering of hydrogen-bonded interfacial water molecules differs substantially at these three interfaces. Specifically, the interfacial water molecules become more disordered (ordered) in mixtures with methanol and ethanol (formic acid), showing higher (lower) vapor pressure than that predicted by Raoult's law.

Disentangling Sum-Frequency Generation Spectra of the Water Bending Mode at Charged Aqueous Interfaces.

The origin of the sum-frequency generation (SFG) signal of the water bending mode has been controversially debated in the past decade. Unveiling the origin of the signal is essential, because different assignments lead to different views on the molecular structure of interfacial water. Here, we combine collinear heterodyne-detected SFG spectroscopy at the water-charged lipid interfaces with systematic variation of the salt concentration. The results show that the bending mode response is of a dipolar, rather than a quadrupolar, nature and allows us to disentangle the response of water in the Stern and the diffuse layers. While the diffuse layer response is identical for the oppositely charged surfaces, the Stern layer responses reflect interfacial hydrogen bonding. Our findings thus corroborate that the water bending mode signal is a suitable probe for the structure of interfacial water.

Remarkable MnO2 structure-dependent H2O promoting effect in HCHO oxidation at room temperature.

H2O is often critical in determining the activity and stability of metal oxide catalysts for HCHO oxidation; however, synthesis of metal oxide catalysts with super resistance to H2O remains a challenging. Herein, we synthesized Akhtenskite-type MnO2 catalyst with Mn-O-Mn stretching along MnO6 octahedra layers, which promotes the utilization of the associatively adsorbed H2O. The activity and stability of formaldehyde oxidation at room temperature enhanced in humid air. Diffuse-reflectance infrared Fourier transform (DRIRFT) spectroscopy was used to characterize the H2O adsorption and intermediate species. The associatively adsorbed H2O promotes the oxidation of formaldehyde to CO2 via the formic acid intermediate. The service life of MnO2 is prolonged due to formic acid generation. MnO2 gradually deactivates when formic acid accumulates and forms formate and hydrogen carbonate species. This study provides significant insights into the development of a high-efficiency MnO2 catalyst for formaldehyde oxidation in humid air, and the developed MnO2 catalyst is a promising candidate for application in practical formaldehyde elimination.

Impact of adolescent obesity on middle-age health of women given data MAR.

We analyze adolescent BMI and middle-age systolic blood pressure (SBP) repeatedly measured on women enrolled in the Fels Longitudinal Study (FLS) between 1929 and 2010 to address three questions: Do adolescent-specific growth rates in body mass index (BMI) and menarche affect middle-age SBP? Do they moderate the aging effect on middle-age SBP? Have the effects changed over historical time? To address the questions, we propose analyzing a growth curve model (GCM) that controls for age, birth-year cohort, and historical time. However, several complications in the data make the GCM analysis nonstandard. First, the person-specific adolescent BMI and middle-age SBP trajectories are unobservable. Second, missing data are substantial on BMI, SBP, and menarche. Finally, modeling the latent trajectories for BMI and SBP, repeatedly measured on two distinct sets of unbalanced time points, are computationally intensive. We adopt a bivariate GCM for BMI and SBP with correlated random coefficients. To efficiently handle missing values of BMI, SBP, and menarche assumed missing at random, we estimate their joint distribution by maximum likelihood via the EM algorithm where the correlated random coefficients and menarche are multivariate normal. The estimated distribution will be transformed to the desired GCM for SBP that includes the random coefficients of BMI and menarche as covariates. We demonstrate unbiased estimation by simulation. We find that adolescent growth rates in BMI and menarche are positively associated with, and moderate, the aging effect on SBP in middle age, controlling for age, cohort, and historical time, but the effect sizes are at most modest. The aging effect is significant on SBP, controlling for cohort and historical time, but not vice versa.

Decoding the molecular water structure at complex interfaces through surface-specific spectroscopy of the water bending mode.

The structure of interfacial water determines atmospheric chemistry, wetting properties of materials, and protein folding. The challenge of investigating the properties of specific interfacial water molecules has frequently been confronted using surface-specific sum-frequency generation (SFG) vibrational spectroscopy using the O-H stretch mode. While perfectly suited for the water-air interface, for complex interfaces, a potential complication arises from the contribution of hydroxyl or amine groups of non-water species present at the surface, such as surface hydroxyls on minerals, or O-H and N-H groups contained in proteins. Here, we present a protocol to extract the hydrogen bond strength selectively of interfacial water, through the water bending mode. The bending mode vibrational frequency distribution provides a new avenue for unveiling the hydrogen bonding structure of interfacial water at complex aqueous interfaces. We demonstrate this method for the water-CaF2 and water-protein interfaces. For the former, we show that this method can indeed single out water O-H groups from surface hydroxyls, and that with increasing pH, the hydrogen-bonded network of interfacial water strengthens. Furthermore, we unveil enhanced hydrogen bonding of water, compared to bulk water, at the interface with human serum albumin proteins, a prototypical bio-interface.