Simultaneous quantification of hyperpolarized xenon-129 ventilation and gas exchange with multi-breath xenon-polarization transfer contrast (XTC) MRI.

PURPOSE: To demonstrate the feasibility of a multi-breath xenon-polarization transfer contrast (XTC) MR imaging approach for simultaneously evaluating regional ventilation and gas exchange parameters. METHODS: Imaging was performed in five healthy volunteers and six chronic obstructive pulmonary disease (COPD) patients. The multi-breath XTC protocol consisted of three repeated schemes of six wash-in breaths of a xenon mixture and four normoxic wash-out breaths, with and without selective saturation of either the tissue membrane or red blood cell (RBC) resonances. Acquisitions were performed at end-exhalation while subjects maintained tidal breathing throughout the session. The no-saturation, membrane-saturation, and RBC-saturation images were fit to a per-breath gas replacement model for extracting voxelwise tidal volume (TV), functional residual capacity (FRC), and fractional ventilation (FV), as well as tissue- and RBC-gas exchange (fMem and fRBC , respectively). The sensitivity of the derived model was also evaluated via simulations. RESULTS: With the exception of FRC, whole-lung averages for all metrics were decreased in the COPD subjects compared to the healthy cohort, significantly so for FV, fRBC , and fMem . Heterogeneity was higher overall in the COPD subjects, particularly for fRBC , fMem , and fRBC:Mem . The anterior-to-posterior gradient associated with the gravity-dependence of lung function in supine imaging was also evident for FV, fRBC , and fMem values in the healthy subjects, but noticeably absent in the COPD cohort. CONCLUSION: Multi-breath XTC imaging generated high-resolution, co-registered maps of ventilation and gas exchange parameters acquired during tidal breathing and with low per-breath xenon doses. Clear differences between healthy and COPD subjects were apparent and consistent with spirometry.

Developing a new national MDMA policy: Results of a multi-decision multi-criterion decision analysis.

BACKGROUND: Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) has a relatively low harm and low dependence liability but is scheduled on List I of the Dutch Opium Act ('hard drugs'). Concerns surrounding increasing MDMA-related criminality coupled with the possibly inappropriate scheduling of MDMA initiated a debate to revise the current Dutch ecstasy policy. METHODS: An interdisciplinary group of 18 experts on health, social harms and drug criminality and law enforcement reformulated the science-based Dutch MDMA policy using multi-decision multi-criterion decision analysis (MD-MCDA). The experts collectively formulated policy instruments and rated their effects on 25 outcome criteria, including health, criminality, law enforcement and financial issues, thematically grouped in six clusters. RESULTS: The experts scored the effect of 22 policy instruments, each with between two and seven different mutually exclusive options, on 25 outcome criteria. The optimal policy model was defined by the set of 22 policy instrument options which gave the highest overall score on the 25 outcome criteria. Implementation of the optimal policy model, including regulated MDMA sales, decreases health harms, MDMA-related organised crime and environmental damage, as well as increases state revenues and quality of MDMA products and user information. This model was slightly modified to increase its political feasibility. Sensitivity analyses showed that the outcomes of the current MD-MCDA are robust and independent of variability in weight values. CONCLUSION: The present results provide a feasible and realistic set of policy instrument options to revise the legislation towards a rational MDMA policy that is likely to reduce both adverse (public) health risks and MDMA-related criminal burden.

Measuring pulmonary gas exchange using compartment-selective xenon-polarization transfer contrast (XTC) MRI.

PURPOSE: To demonstrate the feasibility of generating red blood cell (RBC) and tissue/plasma (TP)-specific gas-phase (GP) depolarization maps using xenon-polarization transfer contrast (XTC) MR imaging. METHODS: Imaging was performed in three healthy subjects, an asymptomatic smoker, and a chronic obstructive pulmonary disease (COPD) patient. Single-breath XTC data were acquired through a series of three GP images using a 2D multi-slice GRE during a 12 s breath-hold. A series of 8 ms Gaussian inversion pulses spaced 30 ms apart were applied in-between the images to quantify the exchange between the GP and dissolved-phase (DP) compartments. Inversion pulses were either centered on-resonance to generate contrast, or off-resonance to correct for other sources of signal loss. For an alternative scheme, inversions of both RBC and TP resonances were inserted in lieu of off-resonance pulses. Finally, this technique was extended to a multi-breath protocol consistent with tidal breathing, involving 30 consecutive acquisitions. RESULTS: Inversion pulses shifted off-resonance by 20 ppm to mimic the distance between the RBC and TP resonances demonstrated selectivity, and initial GP depolarization maps illustrated stark magnitude and distribution differences between healthy and diseased subjects that were consistent with traditional approaches. CONCLUSION: The proposed DP-compartment selective XTC MRI technique provides information on gas exchange between all three detectable states of xenon in the lungs and is sufficiently sensitive to indicate differences in lung function between the study subjects. Investigated extensions of this approach to imaging schemes that either minimize breath-hold duration or the overall number of breath-holds open avenues for future research to improve measurement accuracy and patient comfort.

Sexual, addiction and mental health care needs among men who have sex with men practicing chemsex - a cross-sectional study in the Netherlands.

Drug use during sex ('chemsex') has been associated with sexually transmitted infections (STIs) and mental health harms. Little quantitative evidence exists on the health care needs of MSM practicing chemsex from a patient perspective. This study assessed self-perceived benefits and harms and the needs for professional counselling among MSM practicing chemsex. In 2018, 785 MSM were recruited at nine Dutch STI clinics and 511 (65%) completed the online questionnaire. Chemsex was defined as using cocaine, crystal meth, designer drugs, GHB/GBL, ketamine, speed and/or XTC/MDMA during sex <6 months. Chemsex was reported by 41% (209/511), of whom 23% (48/209) reported a need for professional counselling. The most reported topic to discuss was increasing self-control (52%, 25/48). Most MSM preferred to be counselled by sexual health experts (56%, 27/48). The need for professional counselling was higher among MSM who engaged in chemsex ≥2 times per month (30% vs. 17%, p = 0.03), did not have sex without drugs (sober sex) in the past three months (41% vs. 20%, p = 0.04), experienced disadvantages of chemsex (28% vs. 15%, p = 0.03), had a negative change in their lives due to chemsex (53% vs. 21%, p = 0.002), and/or had an intention to change chemsex behaviours (45% vs. 18%, p < 0.001). Our study shows that almost one in four MSM practicing chemsex expressed a need for professional counselling on chemsex-related issues. STI healthcare providers should assess the need for professional counselling in MSM practicing chemsex, especially in MSM with above mentioned characteristics, such as frequent users.

Overall mean estimation of trace evidence in a two-level normal-normal model.

In the evaluation of measurements on characteristics of forensic trace evidence, Aitken and Lucy (2004) model the data as a two-level model using assumptions of normality where likelihood ratios are used as a measure for the strength of evidence. A two-level model assumes two sources of variation: the variation within measurements in a group (first level) and the variation between different groups (second level). Estimates of the variation within groups, the variation between groups and the overall mean are required in this approach. This paper discusses three estimators for the overall mean. In forensic science, two of these estimators are known as the weighted and unweighted mean. For an optimal choice between these estimators, the within- and between-group covariance matrices are required. In this paper a generalization to the latter two mean estimators is suggested, which is referred to as the generalized weighted mean. The weights of this estimator can be chosen such that they minimize the variance of the generalized weighted mean. These optimal weights lead to a "toy estimator", because they depend on the unknown within- and between-group covariance matrices. Using these optimal weights with estimates for the within- and between-group covariance matrices leads to the third estimator, the optimal "plug-in" generalized weighted mean estimator. The three estimators and the toy estimator are compared through a simulation study. Under conditions generally encountered in practice, we show that the unweighted mean can be preferred over the weighted mean. Moreover, in these situations the unweighted mean and the optimal generalized weighted mean behave similarly. An artificial choice of parameters is used to provide an example where the optimal generalized weighted mean outperforms both the weighted and unweighted mean. Finally, the three mean estimators are applied to real XTC data to illustrate the impact of the choice of overall mean estimator.

Multinucleation of Incubated Cells and Their Morphological Differences Compared to Mononuclear Cells.

Some cells cultured in vitro have multiple nuclei. Since cultured cells are used in various fields of science, including tissue engineering, the nature of the multinucleated cells must be determined. However, multinucleated cells are not frequently observed. In this study, a method to efficiently obtain multinucleated cells was established and their morphological properties were investigated. Initially, we established conditions to quickly and easily generate multinucleated cells by seeding a Xenopus tadpole epithelium tissue-derived cell line (XTC-YF) on less and more hydrophilic dishes, and incubating the cultures with medium supplemented with or without Y-27632-a ROCK inhibitor-to reduce cell contractility. Notably, 88% of the cells cultured on a less hydrophilic dish in medium supplemented with Y-27632 became multinucleate 48 h after seeding, whereas less than 5% of cells cultured under other conditions exhibited this morphology. Some cells showed an odd number (three and five) of cell nuclei 72 h after seeding. Multinucleated cells displayed a significantly smaller nuclear area, larger cell area, and smaller nuclear circularity. As changes in the morphology of the cells correlated with their functions, the proposed method would help researchers understand the functions of multinucleated cells.

Objective color classification of ecstasy tablets by hyperspectral imaging.

The general procedure followed in the examination of ecstasy tablets for profiling purposes includes a color description, which depends highly on the observers' perception. This study aims to provide objective quantitative color information using visible hyperspectral imaging. Both self-manufactured and illicit tablets, created with different amounts of known colorants were analyzed. We derived reflectance spectra from hyperspectral images of these tablets, and successfully determined the most likely colorant used in the production of all self-manufactured tablets and four of five illicit tablets studied. Upon classification, the concentration of the colorant was estimated using a photon propagation model and a single reference measurement of a tablet of known concentration. The estimated concentrations showed a high correlation with the actual values (R(2) = 0.9374). The achieved color information, combined with other physical and chemical characteristics, can provide a powerful tool for the comparison of tablet seizures, which may reveal their origin.

A mesoderm-inducing factor from a Xenopus laevis cell line : Chemical properties and relation to the vegetalizing factor from chicken embryos.

We have compared the chemical properties and biological activities of the mesoderm-inducing factor that is secreted by the Xenopus XTC cell line with the vegetalizing factor from chicken embryos. The inducing activity of the factors was tested in different concentrations on totipotent ectoderm either by implantation into early gastrulae of Triturm alpestris or by application of solutions to isolated ectoderm of early gastrulae of Xenopus laevis. Both factors have similar properties. They are not irreversibly inactivated after treatment with 6 M urea or with phenol at 60° C. Reduction with thioglycolic acid inactivates the factors completely. The inducing activity of XTC-conditioned medium decreases only slightly after treatment with 50% formic acid. The apparent molecular mass and the isoelectric point of the factors are similar. The XTC factor was partially purified by size-exclusion and reversed-phase high-pressure liquid chromatography and by isoelectric focusing. The possible relationship of these factors to transforming growth factor ß is discussed.