Comparison of self-reported measures of alcohol-related dependence among young Swiss men: a study protocol for a cross-sectional controlled sample.

Short screenings of alcohol-related dependence are needed for population-based assessments. A clinical interview constitutes a reliable diagnosis often seen as gold standard, but it is costly and time consuming and as such, not suitable for population-based assessments. Therefore, self-reported questionnaires are needed (eg, alcohol use disorder (AUD) as in the Diagnostic and Statistic Manual of Mental Disorders (DSM) 5), but their reliability is questionable. Recent studies called for more evidence-based measurements for population-based screening (eg, heavy alcohol use over time (HAU)). This study aims to test the reliability of different self-reported measures of alcohol use. Based on stratified random selection, 280 participants will be recruited from the French-speaking subgroup of the Swiss National Science Foundation-supported Cohort Study on Substance Use and Risk Factors (C-SURF). This cohort is a population-based sample of young Swiss men in their mid-20s (n=2668). The sample size calculation is based on a proportion non-inferiority test (alpha=5%, power=80%, margin of equivalence=10%, difference in sensitivity between self-reported AUD and HAU=5%, correlation between AUD and HAU=0.35, and drop-outs=15%). Assessment will include a clinical interview as the gold standard of alcohol-related dependence, self-reported alcohol measures (HAU, AUD and drinking patterns), biomarkers as gold standards of chronic excessive drinking, and health outcomes. To assess the validity of the self-reported alcohol measures, sensitivity analyses will be run. The associations between alcohol-related measures and health outcomes will be tested. A non-response analysis will be run using the previous waves of the C-SURF study using logistic regressions. The study protocol has been approved by the Human Research Ethics Committee of the Canton of Vaud, Switzerland (no. 2017-00776). The results will be submitted for publication in peer-reviewed journals and presented at national and international conferences

Performance of self-reported measures of alcohol use and of harmful drinking patterns against ethyl glucuronide hair testing among young Swiss men.

There is a need for empirical studies assessing the psychometric properties of self-reported alcohol use as measures of excessive chronic drinking (ECD) compared to those of objective measures, such as ethyl glucuronide (EtG). To test the quality of self-reported measures of alcohol use and of risky single-occasion drinking (RSOD) to detect ECD assessed by EtG. A total of 227 samples of hair from young Swiss men were used for the determination of EtG. Self-reported measures of alcohol use (previous twelve-month and previous-week alcohol use) and RSOD were assessed. Using EtG (<30 pg/mg) as the gold standard of ECD assessment, the sensitivity and specificity were computed, and the AUROC were compared for alcohol use measures and RSOD. Logistic regressions were used to test the contribution of RSOD to the understanding of ECD after controlling for alcohol use. A total of 23.3% of participants presented with ECD. Previous twelve-month alcohol use with a cut-off of >15 drinks per week (sensitivity = 75.5%, specificity = 78.7%) and weekly RSOD (sensitivity = 75.5%, specificity = 70.1%) yielded acceptable psychometric properties. No cut-off for previous-week alcohol use gave acceptable results. In the multivariate logistic regression, after controlling for the previous twelve months of alcohol use, RSOD was still significantly associated with EtG (p = .016). Self-reported measures of the previous twelve months of alcohol use and RSOD were acceptable measures of ECD for population-based screening. Self-reported RSOD appeared to be an interesting screening measure, in addition to the previous twelve months of alcohol use, to understand ECD among young people

A Fatal Overdose of Cocaine Associated with Coingestion of Marijuana, Buprenorphine, and Fluoxetine. Body Fluid and Tissue Distribution of Cocaine and Its Metabolites Determined by Hydrophilic Interaction Chromatography-Mass Spectrometry (HILIC-MS)

Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 μL pure acetonitrile and 5 μL was directly injected onto a Waters Atlantis™ HILIC 150- × 2.1-mm, 3-μm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below ± 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 μg/L) were also discovered. A relatively high concentration of Δ9-THC was measured both in peripheral blood (8.2 μg/L) and brain cortex (13.5 μg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoid

App Personalization with Images Generated Using Artificial Intelligence

Personalized content such as app backgrounds, profile pictures, etc. help in creating a rich and interactive user experience for an app, potentially driving an increase in the active usage. Recent advancements in generative imagery can be used to generate images that are personalized to the user. However, current image generation techniques require a user to explicitly provide prompts to the generation model. This disclosure describes techniques that use generative artificial intelligence to automatically generate customized images for use as an app background or in other contexts. Prompts for image creation are generated based on user-permitted contextual information by using a large language model or other technique. The generated images are filtered by an image recommendation model and provided for user selection to customize the app experience

Simultaneous and Sensitive Analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in Plasma after Oral Application of Small Doses of THC and Cannabis Extract

Besides the psychoactive Δ9-tetrahydrocannabinol (THC), hashish and marijuana as well as cannabis-based medicine extracts contain varying amounts of cannabidiol (CBD) and of the degradation product cannabinol (CBN). The additional determination of these compounds is interesting from forensic and medical points of view because it can be used for further proof of cannabis exposure and because CBD is known to modify the effects of THC. Therefore, a method for the simultaneous quantitative determination of THC, its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH), CBD and CBN from plasma was developed. The method was based on automatic solid-phase extraction with C18 ec columns, derivatization with N,O-bistrimethylsilyltrifluoroacetamide (BSTFA), and gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS) with deuterated standards. The limits of detection were between 0.15 and 0.29 ng/mL for THC, 11-OH-THC, THC-COOH, and CBD and 1.1 ng/mL for CBN. The method was applied in a prospective pharmacokinetic study after single oral administration of 10 mg THC alone or together with 5.4 mg CBD in cannabis extract. The maximum plasma concentrations after cannabis extract administration ranged between 1.2 and 10.3 ng/mL (mean 4.05 ng/mL) for THC, 1.8 and 12.3 ng/mL (mean 4.9 ng/mL) for 11-OH-THC, 19 and 71 ng/mL (mean 35 ng/mL) for THC-COOH, and 0.2 and 2.6 ng/mL (mean 0.95 ng/mg) for CBD. The peak concentrations (mean values) of THC, 11-OH-THC, THC-COOH, and CBD were observed at 56, 82, 115, and 60 min, respectively, after intake. CBN was not detected. Caused by the strong first-pass metabolism, the concentrations of the metabolites were increased during the first hours after drug administration when compared to literature data for smoking. Therefore, the concentration ratio 11-OH-THC/THC was discussed as a criterion for distinguishing oral from inhalative cannabis consumptio

A systematic review of passive exposure to cannabis

Passive exposure to cannabis smoke may induce effects on behavior and psychomotor skills, and have legal consequences, including the risk of being falsely considered as a cannabis user. This can become a concern, especially in occupational contexts or when driving vehicles. In order to enable a differentiation between a passive and an active exposure to cannabis and to limit the likeliness to be detected positive following passive exposure, this review identified specific biomarkers of passive exposure in urine, blood, oral fluid, hair, and sebum. Out of 958 papers identified on passive exposure to cannabis, 21 were selected. Although positive tests had been observed in all matrices following extremely high passive exposure, some distinctive features were observed in each matrix compared to cannabis active use. More specifically, in everyday life conditions, 11-nor-delta-9-THC-carboxylic acid (THC-COOH) urinary level should be detected below the positivity threshold used to confirm active smoking of cannabis, especially after normalization to creatinine level. Measuring delta-9-tetrahydrocannabinol (THC) and THC-COOH in blood is an appropriate alternative for appraising passive exposure as low and very low concentrations of THC and THC-COOH, respectively, should be measured. In hair, oral fluid (OF) and sweat/sebum emulsion, no THCCOOH should be detected. Its presence in hair argues for regular cannabis consumption and in OF or sweat for recent consumption. The experts should recommend to persons who have to demonstrate abstinence from cannabis to avoid heavily smoky and unventilated environments

Diagnostic performance of ethyl glucuronide in hair for the investigation of alcohol drinking behavior: a comparison with traditional biomarkers

Background: Ethyl glucuronide (EtG) in hair has emerged as a useful biomarker for detecting alcohol abuse and monitoring abstinence. However, there is a need to establish a reliable cutoff value for the detection of chronic and excessive alcohol consumption. Methods: One hundred and twenty-five subjects were classified as teetotalers, low-risk drinkers, at-risk drinkers, or heavy drinkers. The gold standard for subjects' classifications was based on a prospective daily alcohol self-monitoring log. Subjects were followed for a 3-month period. The EtG diagnostic performance was evaluated and compared with carbohydrate-deficient transferring (CDT) and the activities of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl-transferase (γGT). Results: A cutoff of >9pg/mg EtG in hair, suggesting an alcohol consumption of >20/30g (at-risk drinkers), and a cutoff of >25pg/mg, suggesting a consumption of >60g (heavy drinkers), were determined by receiver operating characteristic analysis. The EtG diagnostic performance was significantly better (P < 0.05) than any of the traditional biomarkers alone. EtG, as a single biomarker, yielded a stronger or similar diagnostic performance in detecting at-risk or heavy drinkers, respectively, than the best combination of traditional biomarkers (CDT and γGT). The combination of EtG with traditional biomarkers did not improve the diagnostic performance of EtG alone. EtG demonstrated a strong potential to identify heavy alcohol consumption, whereas the traditional biomarkers failed to do so. EtG was not significantly influenced by gender, body mass index, or age. Conclusion: Hair EtG definitively provides an accurate and reliable diagnostic test for detecting chronic and excessive alcohol consumption. The proposed cutoff values can serve as reference for future cutoff recommendations for clinical and forensic us

Codeine accumulation and elimination in larvae, pupae, and imago of the blowfly Lucilia sericata and effects on its development

The aim of this study was to evaluate the reliability of insect larvae as samples for toxicological investigations. For this purpose, larvae of Lucilia sericata were reared on samples of minced pig liver treated with different concentrations of codeine: therapeutic, toxic, and potentially lethal doses. Codeine was detected in all tested larvae, confirming the reliability of these specimens for qualitative toxicology analysis. Furthermore, concentrations measured in larvae were correlated with levels in liver tissue. These observations bring new elements regarding the potential use of opiates concentrations in larvae for estimation of drug levels in human tissues. Morphine and norcodeine, two codeine metabolites, have been also detected at different concentrations depending on the concentration of codeine in pig liver and depending on the substance itself. The effects of codeine on the development of L. sericata were also investigated. Results showed that a 29-h interval bias on the evaluation of the larval stage duration calculated from the larvae weight has to be considered if codeine was present in the larvae substrate. Similarly, a 21-h interval bias on the total duration of development, from egg to imago, has to be considered if codeine was present in the larvae substrat