Attitudes and perceived social norms towards drug use among gay and bisexual men in Australia

Background: Gay and bisexual men (GBM) report distinctive patterns and contexts of drug use, yet little has been published about their attitudes towards drug use. Objectives: We developed measures of attitudes and perceived social norms towards drug use, and examined covariates of more accepting attitudes and norms among GBM in Australia. Methods: We analysed baseline data from the [removed for blinded review] study. This is an online prospective observational study of drug use among Australian GBM. We used principal components factor analysis to generate two attitudinal scales assessing “drug use for social and sexual enhancement” and “perceptions of drug risk”. A third perceived social norms scale examined “acceptability of drug use among gay friends”. Results: Among 2,112 participants, 61% reported illicit drug use in the preceding 6 months. Stronger endorsement of drug use for social and sexual engagement and lower perceptions of drug risk were found among men who were more socially engaged with other gay men and reported regular drug use and drug use for sex. In multivariate analyses, all three scales were associated with recent drug use (any use in the previous six months), but only the drug use for social and sexual enhancement scale was associated with regular (at least monthly) use. Conclusions: Drug use and sex are difficult to disentangle for some GBM, and health services and policies could benefit from a better understanding of attitudinal and normative factors associated with drug use in gay social networks, while recognising the role of pleasure in substance use

Wide operational windows of edge-localized mode suppression by resonant magnetic perturbations in the DIII-D tokamak

Edge-Localized-Mode (ELM) suppression by resonant magnetic perturbations (RMPs) generally occurs over very narrow ranges of the plasma current (or magnetic safety factor q95) in the DIII-D tokamak. However, wide q95 ranges of ELM suppression are needed for the safety and operational flexibility of ITER and future reactors. In DIII-D ITER Similar Shape (ISS) plasmas with n=3 RMPs, the range of q95 for ELM suppression is found to increase with decreasing electron density. Nonlinear two-fluid MHD simulations reproduce the observed q95 windows of ELM suppression and the dependence on plasma density, based on the conditions for resonant field penetration at the top of the pedestal. When the RMP amplitude is close to the threshold for resonant field penetration, only narrow isolated magnetic islands form near the top of the pedestal, leading to narrow q95 windows of ELM suppression. However, as the threshold for field penetration decreases with decreasing density, resonant field penetration can take place over a wider range of q95. For sufficiently low density (penetration threshold) multiple magnetic islands form near the top of the pedestal giving rise to continuous q95 windows of ELM suppression. The model predicts that wide q95 windows of ELM suppression can be achieved at substantially higher pedestal pressure in DIII-D by shifting to higher toroidal mode number (n=4) RMPs

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype

Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses

Background: 18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT. Methods: Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12). Results: No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 � 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial. Conclusion: This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously.This study was supported by NIH grant R01 CA115559, 1R01 CA107264, and 1R01 CA80907

Interlayer Registry Determines the Sliding Potential of Layered Metal Dichalcogenides: The case of 2H-MoS2

We provide a simple and intuitive explanation for the interlayer sliding energy landscape of metal dichalcogenides. Based on the recently introduced registry index (RI) concept, we define a purely geometrical parameter which quantifies the degree of interlayer commensurability in the layered phase of molybdenum disulphide (2HMoS2). A direct relation between the sliding energy landscape and the corresponding interlayer registry surface of 2H-MoS2 is discovered thus marking the registry index as a computationally efficient means for studying the tribology of complex nanoscale material interfaces in the wearless friction regime.Comment: 13 pages, 7 figure