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We previously showed that ketogenic diet (KD) was effective in curbing alcohol withdrawal and craving in individuals with alcohol use disorder (AUD). We hypothesized that the clinical benefits were due to improvements in sleep. To test this, we performed a secondary analysis on the KD trial data to (1) examine the effects of KD on total sleep time (TST) and sleep quality and (2) investigate the association between KD-induced alterations in cingulate glutamate concentration and changes in TST and sleep quality.AUD individuals undergoing alcohol detoxification were randomized to receive KD (n=19) or standard American diet (SA; n=14) for three weeks. TST was measured weekly by self-report, GENEActive sleep accelerometer, and X4 Sleep Profiler ambulatory device. Sleep quality was assessed using subjectively ratings of sleep depth and restedness and Sleep Profiler (Sleep Efficiency [%]). WeeklyTST was lower in KD than SA and increased with effect of time. Sleep depth, restedness, and Sleep Efficiency improved with time, but exhibited no effect of diet. In KD and SA combined, week 1 cingulate glutamate levels correlated positively with Sleep Efficiency, but not with TST.Although cingulate glutamate levels correlated positively with Sleep Efficiency in week 1, KD-induced glutamate elevation did not produce significant sleep improvements. Rather, KD was associated with lower TST than SA. Given the well-established associations between sleep and alcohol relapse, longer follow up assessment of KD's impact on sleep in AUD is warranted.

Constitutive models constructed within the combined framework of kinematic hardening and bounding surface plasticity have proved to be successful in describing the rate-independent deformation of soils under non-monotonic histories of stress or strain. Most soils show some rate-dependence of their deformation characteristics, and it is important for the constitutive models to be able to reproduce rate- or time-dependent patterns of response. This paper explores a constitutive modelling approach that combines multiple viscoplastic mechanisms contributing to the overall rate-sensitive deformation of a soil. A simple viscoplastic extension of an inviscid kinematic hardening model incorporates two viscoplastic mechanisms applying an overstress formulation to a ‘consolidation surface’ and a ‘recent stress history surface’. Depending on the current stress state and the relative ‘strength’ of the two mechanisms, the viscoplastic mechanisms may collaborate or compete with each other. This modelling approach is shown to be able to reproduce many observed patterns of rate-dependent response of soils.

Graphic warning labels (GWLs) on cigarette packs have been adopted by many jurisdictions worldwide. In the US, the introduction of GWLs has been delayed by claims that their high level of negative emotional arousal unnecessarily infringed on the tobacco manufacturers' free speech. This study aimed to provide experimental data on the contribution of emotional arousal to GWL efficacy.Observational study using long-term naturalistic exposure and functional magnetic resonance imaging.Research university in Philadelphia, PA, USA.168 adult smokers.For 4 weeks, participants received cigarettes in packs that carried either high-arousal or low-arousal GWLs (N=84 vs. 84). Smoking behavior, quitting-related cognitions and GWL-induced brain response were measured before and after the 4-week exposure. The amygdala and medial prefrontal cortex served as regions of interest.Compared with the high-arousal group, the low-arousal group smoked fewer cigarettes (log10-transformed, 1.076 vs. 1.019; difference=0.056, 95% confidence interval=[0.027,0.085], χHigh-arousal cigarette graphic warning labels (GWLs) appear to be less efficacious than low-arousal GWLs. The high emotional reaction that high-arousal GWLs elicit wanes over time. Baseline amygdala response negatively predicts efficacy of high-arousal GWLs and positively predicts efficacy of low-arousal GWLs. High emotional arousal may not be required for GWLs' sustained efficacy.

Since 1991, China implemented the reform of the old age insurance system for urban enterprise employees, the work of establishing a multi-level old-age insurance system has been carried on continuously, and the three-pillar old-age insurance system is developing vigorously. By introducing the development process of China's pension insurance, this paper analyzes the construction process of the three-pillar system, and combined with the current background of China's aging population, puts forward the problems existing in the system, and gives corresponding suggestions, so as to promote the improvement and development of the three-pillar system of pension insurance, and improve China's comprehensive pension capacity.

This paper presents a soil-water retention curve (SWRC) model for fine-grained soils. Compared with existing studies, the proposed model accounts for the distinct roles of the volume change of soils on capillarity and adsorption mechanisms. The capillary water is described by a relation that includes the characteristics of the pore-size distributions as parameters, while the absorbed water is modeled by a novel proposition that both considers the phenomenon of capillary condensation and allows for the decoupling between the degree of capillary and adsorptive saturation. Based on this feature, the void ratio effects are considered in a way in which they only affect capillary water, i.e., consistent with how volume change influences soil microstructures. The relative contributions of void ratio effects and hydraulic hysteresis on the path- and history-dependence of a SWRC in Sr–s–e space, where Sr is degree of saturation, s is matric suction, e is void ratio, for deformable unsaturated soils are examined. The significance of discriminating the effects of volume change on capillary and adsorptive water is illustrated by applying the SWRC model to computing the shear strength of unsaturated soils with different void ratios. The model performance is assessed by comparing against test data reported for four types of fine-grained soils in the literature and those tested for natural loess in this work.

Environmental qualification (EQ) is a process to ensure that equipment will be capable of withstanding the ambient conditions and executing specific function that the equipment is actually called upon to be performed under accident conditions. The main purpose of EQ is to provide reasonable evidence to ensure that common cause failures will not occur. Electric penetration assemblies (EPAs) belong to EQ components and perform safety-related functions. The time limited aging analysis (TLAA) of EQ components includes all long-lived, passive and active electrical components and commodities located in a harsh environment that are important to safety. This paper takes the electric penetration assembly (EPA) of a early domestic M310 NPP as the research object, based on the components, materials, environment, aging mechanisms and effects of EPA, combined with domestic and foreign standards, specifications and latest research results of equipment qualification and operation license extension, the time limited aging analysis key method of EPA of a early domestic M310 NPP is studied, the test scheme is designed, the test sample is selected, the key parameters are determined, the supplementary environmental qualification of EPA of a early domestic M310 NPP is finished. At the same time, combined with the current management status of EQ equipment at home and abroad, some management suggestions are proposed to maintain the validity of the qualification status during the period of operation license extension.

This work presents a spherical cavity expansion solution aimed at linking soil constitutive behavior with quantities that bear direct engineering meanings for practicing engineers (e.g., foundation bearing capacity). For this purpose, we derive the solution based on the state-dependent, critical state constitutive model proposed by Li and Dafalias (Geotechnique 50(4): 449–460, 2000), whose ability to realistically represent the actual mechanical behavior of sand has been extensively verified in the literature. To ensure the reliability of the solution, we verify it against an independent finite element analysis of spherical cavity expansion in solid governed by the same constitutive model. In this validation, we also highlight the dependence of cavity expansion response on the current state of granular materials relative to critical state. The application of the proposed solution in solving engineering problems is demonstrated in predicting the resistance of cone penetration and the ground movements associated with static pipe bursting in sand. We show that, based on the soil parameters determined from laboratory triaxial tests, the proposed solution can reasonably represent the dependence of cone penetration resistance on the density and pressure level of sand, as revealed from centrifuge testing. By comparing with finite element analysis, we demonstrate that the proposed solution can provide useful estimations for soil displacements caused by pipe bursting operation. These archetypal examples suggest that the proposed cavity expansion solution can form a theoretical basis for linking fundamental soil properties with quantities that have direct implications for geotechnical engineering practice.

This paper presents an analytical three-dimensional rotational mechanism for the limit analysis on the overall stability of slurry trenches in layered cohesive soils. The proposed mechanis...

The mechanical response of natural clays can exhibit significant directional dependence due to loading history and layered soil structure. We report an experimental investigation of the st...

Although recent research has suggested that reminders of mortality may increase behaviors and cognitions associated with escaping the self, this notion has not been directly tested. The current work provides evidence that mortality salience (MS) decreases the brain activity in response to the encoding of self-referential memory (Experiment 1) and impairs subsequent retrieval of self-referential memory (Experiment 2). Experiment 1 (N = 39) used event-related potentials to examine participants’ brain response while they performed trait judgments about the self and a celebrity, after they were primed with either MS or death-irrelevant negative affect (NA). Relative to NA, MS priming significantly attenuated an early frontal positivity at 180–300 ms in response to self- vs. celebrity-referential encoding. In Experiment 2 (N = 177), MS- and NA-primed participants performed the above trait judgment tasks and then completed a recognition test for the previously presented trait adjectives. Relative to NA priming, MS priming impaired recognition of trait adjectives that were associated with the self but not the celebrity. Overall, our findings suggest impaired self-referential processing, or ‘escaping’ the self, as a coping strategy for mortality concerns.

Adherence is a major factor in the effectiveness of the injectable extended-release naltrexone as a relapse prevention treatment in opioid use disorder. We examined the value of a variant of the Go/No-go paradigm in predicting extended-release naltrexone adherence in 27 detoxified opioid use disorder patients who were offered up to 3 monthly extended-release naltrexone injections. Before extended-release naltrexone, participants performed a Go/No-go task that comprised positively valenced Go trials and negatively valenced No-go trials during a functional magnetic resonance imaging scan. Errors of commission and neural responses to the No-go vs Go trials were independent variables. Adherence, operationalized as the completion of all 3 extended-release naltrexone injections, was the outcome variable. Fewer errors of commission and greater left accumbal response during the No-go vs Go trials predicted better adherence. These findings support the clinical potential of the behavioral and neurophysiological correlates of response inhibition in the prediction of extended-release naltrexone treatment outcomes in opioid use disorder.

IntroductionMentholated tobacco cigarettes are believed to be more addictive than non-menthol ones. Packaging of most menthol cigarette brands includes distinctive green hues, which may act as conditioned stimuli (ie, cues) and promote menthol smoking. To examine the cue properties of menthol cigarette packaging, we used a priming paradigm to assess the effect of packaging on the neural substrates of smoking cue reactivity. We hypothesised that menthol packaging will exert a specific priming effect potentiating smoking cue reactivity in menthol compared with non-menthol smokers.MethodsForty-two menthol and 33 non-menthol smokers underwent functional MRI while viewing smoking and neutral cues. The cues were preceded (ie, primed) by briefly presented images of menthol or non-menthol cigarette packages. Participants reported craving for cigarettes in response to each cue.ResultsMenthol packaging induced greater frontostriatal and occipital smoking cue reactivity in menthol smokers than in non-menthol smokers. Menthol packaging also enhanced the mediation by neural activity of the relationship between cue exposure and cigarette craving in menthol but not non-menthol smokers. Dynamic causal modelling showed stronger frontostriatal-occipital connectivity in response to menthol packaging in menthol compared with non-menthol smokers. The effects of non-menthol packaging did not differ between categories of smokers.ConclusionsOur findings demonstrate heightened motivational and perceptual salience of the green-hued menthol cigarette packaging that may exacerbate menthol smokers’ susceptibility to smoking cues. These effects could contribute to the greater addiction severity among menthol smokers and could be considered in the development of science-based regulation and legal review of tobacco product marketing practices.

Highlights • Cortical hypoactivity during inhibitory control predicted greater opioid use severity. • Frontoparietal brain networks significantly contributed to the prediction of severity. • Brain marker of severity predicted subsequent on-treatment opioid craving. • Brain marker predicted on-treatment craving better than clinical severity did., Opioid use disorder (OUD) is characterized by emotional and cognitive impairements that are associated with poor treatment outcomes. The present study investigated the neural mechanism underlying emotion evaluation and inhibitory control using an affective go/no-go (AGN) task and its association with drug use severity and craving in patients with OUD. Twenty-six recently detoxified patients with OUD underwent functional magnetic resonance imaging (fMRI) while performing the AGN task that required response to frequently presented appetitive stimuli (“go”) and inhibition of response to infrequently presented aversive stimuli (“no-go”). The fMRI session was immediately followed by an injection of extended-release opioid antagonist naltrexone (XR-NTX). Participants’ opioid craving was assessed immediately before fMRI and 10 ± 2 days after XR-NTX injection. Multivariate pattern analysis (MVPA) showed that drug use severity was associated with distributed brain hypoactivity in response to aversive no-go stimuli, with particularly large negative contributions from the cognitive control and dorsal attention brain networks. While drug use severity and its associated MVPA brain response pattern were both correlated with opioid craving at baseline, only the brain response pattern predicted craving during XR-NTX treatment. Our findings point to widespread functional hypoactivity in the brain networks underlying emotional inhibitory control in OUD. Such a distributed pattern is consistent with the multifaceted nature of OUD, which affects multiple brain networks. It also highlights the utility of the multivariate approach in uncovering large-scale cortical substrates associated with clinical severity in complex psychiatric disorders and in predicting treatment response.

Opioid use disorder (OUD) is characterized by heightened cognitive, physiological, and neural responses to opioid-related cues that are mediated by mesocorticolimbic brain pathways. Craving and withdrawal are key symptoms of addiction that persist during physiological abstinence. The present study evaluated the relationship between the brain response to drug cues in OUD and baseline levels of craving and withdrawal. We used functional magnetic resonance imaging (fMRI) to examine brain responses to opioid-related pictures and control pictures in 29 OUD patients. Baseline measures of drug use severity, opioid craving, and withdrawal symptoms were assessed prior to cue exposure and correlated with subsequent brain responses to drug cues. Mediation analysis was conducted to test the indirect effect of drug use severity on brain cue reactivity through craving and withdrawal symptoms. We found that baseline drug use severity and opioid withdrawal symptoms, but not craving, were positively associated with the neural response to drug cues in the nucleus accumbens, orbitofrontal cortex, and amygdala. Withdrawal, but not craving, mediated the effect of drug use severity on the nucleus accumbens' response to drug cues. We did not find similar effects for the neural responses to stimuli unrelated to drugs. Our findings emphasize the central role of withdrawal symptoms as the mediator between the clinical severity of OUD and the brain correlates of sensitization to opioid-related cues. They suggest that in OUD, baseline withdrawal symptoms signal a high vulnerability to drug cues.

Single-gravity (1-g) small-scale testing is a widely used method to investigate geomechanics problems that involve the interactions between soils and objects (e.g., structures or machine parts). This letter presents a new approach for performing 1-g model tests where a six-axis industrial robot functions as a versatile actuator capable of moving objects along virtually arbitrary trajectories, while simultaneously tracking multiple components of force and moment acting on the objects. A performance evaluation confirms that the robot's motion control and force measurement are sufficiently accurate for geotechnical model tests. This assessment is completed through two benchmarking exercises: (1) determining the failure envelope of a strip foundation subjected to combined loading and (2) quantifying the force-displacement history for the soil cutting process (e.g., for applications in soil-machine interaction).

The prevalence of tobacco cigarette smoking in the US has declined to approximately 15%, yet, it remains over 90% among individuals with opioid use disorder regardless of whether they are currently using opioids illicitly or as opioid substitution therapy. This disparity raises the question of whether opioids facilitate smoking among individuals with opioid use disorder and whether opioid antagonists may reduce it.Determine whether injectable extended-release naltrexone (XR-NTX) treatment of opioid use disorder patients is associated with a spontaneous smoking reduction. We hypothesized that treatment with XR-NTX for would lead to a reduction in smoking in tobacco cigarette smokers with opioid use disorder.We analyzed data from 64 tobacco cigarette smokers (38% female) with opioid use disorder who were induced on XR-NTX for prevention of relapse to opioids. The number of cigarettes smoked per day and opioid-related craving and withdrawal were assessed at baseline and during treatment.Smoking was reduced from 14.4 ± 1.0 to 9.8 ± 1.0(p0.001) cigarettes per day after one month and 8.6 ± 1.1 cigarettes per day after two months of treatment. Daily cigarette consumption was positively correlated with the pre-treatment frequency of opioid use and opioid-related craving during the XR-NTX treatment.XR-NTX treatment in smokers with opioid use disorder was associated with a 29% decline in daily cigarette consumption. Together with prior evidence of increased smoking during opioid agonist therapy, our finding suggests a pharmacodynamic interaction between nicotine and opioid systems that could influence treatment choices in this population. Our findings merit confirmation in a prospective controlled study. (NCT02324725 and NCT01587196).

Potential damages to existing tunnels represent a major concern for constructing deep excavations in urban areas. The uncertainty of subsurface conditions and the nonlinear interactions between multiple agents (e.g., soils, excavation support structures, and tunnel structures) make the prediction of the response of tunnel induced by adjacent excavations a rather difficult and complex task. This paper proposes an initiative to solve this problem by using process-based modelling, where information generated from the interaction processes between soils, structures, and excavation activities is utilized to gradually reduce uncertainty related to soil properties and to learn the interaction patterns through machine learning techniques. To illustrate such a concept, this paper presents a simple process-based model consisting of artificial neural network (ANN) module, inverse modelling module, and mechanistic module. The ANN module is trained to learn and recognize the patterns of the complex interactions between excavation deformations, its geometries and support structures, and soil properties. The inverse modelling module enables a gradual reduction of uncertainty associated with soil characterizations by accumulating field observations during the construction processes. Based on the inputs provided by the former two modules, the mechanistic module computes the response of tunnel. The effectiveness of the proposed process-based model is evaluated against high-fidelity numerical simulations and field measurements. These evaluations suggest that the strategy of combining artificial intelligence techniques with information generated during interaction processes can represent a promising approach to solve complex engineering problems in conventional industries.