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The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCUgene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure.

The article treats the existence of standing waves and solutions to gradient-flow equation for the Landau–De Gennes models of liquid crystals, a state of matter intermediate between the solid state and the liquid one. The variables of the general problem are the velocity field of the particles and the Q-tensor, a symmetric traceless matrix which measures the anisotropy of the material. In particular, we consider the system without the velocity field and with an energy functional unbounded from below. At the beginning we focus on the stationary problem. We outline two variational approaches to get a critical point for the relative energy functional: by the Mountain Pass Theorem and by proving the existence of a least energy solution. Next we describe a relationship between these solutions. Finally we consider the evolution problem and provide some Strichartz-type estimates for the linear problem. By several applications of these results to our problem, we prove via contraction arguments the existence of local solutions and, moreover, global existence for initial data with small L2-norm.

AbstractIntroduction:Burnout is present at a high rate in emergency medicine. The ambulance driver-rescuers, who furnish first aid to the victims, are the non-medical part of the Italian 118-service staff. There is a lack of research on burnout risk in Italian Emergency Medical Services and, particularly, for this category of workers. The two Italian studies, including a little group of ambulance driver-rescuers, reported inconsistent findings.Hypothesis:This survey investigated for the first time the prevalence and exact profile of burnout in a large sample of Italian driver-rescuers. As a secondary aim, the study described how the items of the Italian version of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) cluster in components in this sample.Methods:This cross-sectional census survey was conducted from June 2015 through May 2016 and involved all the driver-rescuers operating in Sicily, the biggest and most southern region of Italy. The subjects received a classification according to different profiles of burnout by using the Italian version of the MBI-HSS (burnout, engagement, disengagement, over-extension, and work-inefficacy). In order to explore the existence of independent factors, a Principal Component Analysis (PCA) was conducted on the survey to obtain eigenvalues >one for each component in the data.Results:The final sample comprised 2,361 responders (96.6% of the initial sample). Of them, 29.8% were in burnout (95% confidence interval [CI], 27.8% to 31.8%) and 1.7% presented a severe form (95% CI, 1.1% to 2.3%); 30.0% were engaged in their work (95% CI, 21.0% to 34.8%), 24.7% of responders were disengaged (95% CI, 22.9% to 26.5%), 1.2% presented an over-extension profile (95% CI, 0.8% to 1.7%), and 12.6% felt work-inefficacy (95% CI, 11.3% to 14.1%). The factors loaded into a five-factor solution at PCA, explaining 48.1% of the variance and partially replicating the three-factor structure. The Emotional Exhaustion (EE) component was confirmed. New dimensions from Personal Accomplishment (PA) and Depersonalization (DP) sub-scales described empathy and disengagement with patients, respectively, and were responsible for the increased risk of burnout.Conclusions:These results endorse the importance of screening and psychological interventions for this population of emergency workers, where burnout could manifest itself more insidiously. It is also possible to speculate that sub-optimal empathy skills could be related to the disengagement and work-inefficacy feelings registered.

Structural integrity plays an important role in any industrial activity, due to its capability of assessing complex systems against sudden and unpredicted failures. The work here presented investigates an unexpected new mechanism occurring in structures subjected to monotonic and cyclic loading at high temperature creep condition. An unexpected accumulation of plastic strain is observed to occur, within the high-temperature creep dwell. This phenomenon has been observed during several full inelastic finite element analyses. In order to understand which parameters make possible such behaviour, an extensive numerical study has been undertaken on two different notched bars. The notched bar has been selected due to its capability of representing a multiaxial stress state, which is a practical situation in real components. Two numerical examples consisting of an axisymmetric v-notch bar and a semi-circular notched bar are considered, in order to investigate different notches severity. Two material models have been considered for the plastic response, which is modelled by both Elastic-Perfectly Plastic and Armstrong-Frederick kinematic hardening material models. The high-temperature creep behaviour is introduced using the time hardening law. To study the problem several results are presented, as the effect of the material model on the plastic strain accumulation, the effect of the notch severity and the mesh element type and sensitivity. All the findings further confirm that the phenomenon observed is not an artefact but a real mechanism, which needs to be considered when assessing off-design condition. Moreover, it might be extremely dangerous if the cyclic loading condition occurs at such a high loading level.

ABSTRACTStructural integrity plays an important role in any industrial activity, due to its capability of assessing complex systems against sudden and unpredicted failures. The work here presented investigates an unexpected new mechanism occurring in structures subjected to monotonic and cyclic loading at high temperature creep condition. An unexpected accumulation of plastic strain is observed to occur, within the high-temperature creep dwell. This phenomenon has been observed during several full inelastic finite element analyses. In order to understand which parameters make possible such behaviour, an extensive numerical study has been undertaken on two different notched bars. The notched bar has been selected due to its capability of representing a multiaxial stress state, which is a practical situation in real components. Two numerical examples consisting of an axisymmetric v-notch bar and a semi-circular notched bar are considered, in order to investigate different notches severity. Two material models have been considered for the plastic response, which is modelled by both Elastic-Perfectly Plastic and Armstrong-Frederick kinematic hardening material models. The high-temperature creep behaviour is introduced using the time hardening law. To study the problem several results are presented, as the effect of the material model on the plastic strain accumulation, the effect of the notch severity and the mesh element type and sensitivity. All the findings further confirm that the phenomenon observed is not an artefact but a real mechanism, which needs to be considered when assessing off-design condition. Moreover, it might be extremely dangerous if the cyclic loading condition occurs at such a high loading level.

Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder.

As the energy demand increases the power industry has to enhance both efficiency and environmental sustainability of power plants by increasing the operating temperature. The accurate creep fatigue life assessment is important for the safe operation and design of current and future power plant stations. This paper proposes a practical creep fatigue life assessment case of study by the Linear Matching Method (LMM) framework. The LMM for extended Direct Steady Cycle Analysis (eDSCA) has been adopted to calculate the creep fatigue responses due to the cyclic loading under high temperature conditions. A pipe intersection with dissimilar material joint, subjected to high cycling temperature and constant pressure steam, is used as an example. The closed end condition is considered at both ends of main and branch pipes. The impact of the material mismatch, transitional thermal load, and creep dwell on the failure mechanism and location within the intersection is investigated. All the results demonstrate the capability of the method, and how a direct method is able to support engineers in the assessment and design of high temperature component in a complex loading scenario.