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

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

IRAK4 mediates colitis-induced tumorigenesis and chemoresistance in colorectal cancer

Aberrant activation of the NF-κB transcription factors underlies chemoresistance in various cancer types, including colorectal cancer (CRC). Targeting the activating mechanisms, particularly with inhibitors to the upstream IκB kinase (IKK) complex, is a promising strategy to augment the effect of chemotherapy. However, clinical success has been limited, largely because of low specificity and toxicities of tested compounds. In solid cancers, the IKKs are driven predominantly by the Toll-like receptor (TLR)/IL-1 receptor family members, which signal through the IL-1 receptor-associated kinases (IRAKs), with isoform 4 (IRAK4) being the most critical. The pathogenic role and therapeutic value of IRAK4 in CRC have not been investigated. We found that IRAK4 inhibition significantly abrogates colitis-induced neoplasm in APCMin/+ mice, and bone marrow transplant experiments showed an essential role of IRAK4 in immune cells during neoplastic progression. Chemotherapy significantly enhances IRAK4 and NF-κB activity in CRC cells through upregulating TLR9 expression, which can in turn be suppressed by IRAK4 and IKK inhibitors, suggesting a feed-forward pathway that protects CRC cells from chemotherapy. Lastly, increased tumor phospho-IRAK4 staining or IRAK4 mRNA expression is associated with significantly worse survival in CRC patients. Our results support targeting IRAK4 to improve the effects of chemotherapy and outcomes in CRC

Explaining Cold-Pulse Dynamics in Tokamak Plasmas Using Local Turbulent Transport Models

A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. This Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and time scales of cold-pulse experiments in tokamak plasmas.United States. Department of Energy (Award DE-FC02-99ER54512)United States. Department of Energy (Grant DESC0014264

Application of ECH to the Study of Transport in ITER Baseline Scenario-like Discharges in DIII-D

Recent DIII-D experiments in the ITER Baseline Scenario (IBS) have shown strong increases in fluctuations and correlated reduction of confinement associated with entering the electron-heating-dominated regime with strong electron cyclotron heating (ECH). The addition of 3.2 MW of 110 GHz EC power deposited at ρ~0.42 to IBS discharges with ~3 MW of neutral beam injection causes large increases in low-k and medium-k turbulent density fluctuations observed with Doppler backscatter (DBS), beam emission spectroscopy (BES) and phase-contrast imaging (PCI) diagnostics, correlated with decreases in the energy, particle, and momentum confinement times. Power balance calculations show the electron heat diffusivity χ[subscript e] increases significantly in the mid-radius region 0.4<ρ<0.8, which is roughly the same region where the DBS and BES diagnostics show the increases in turbulent density fluctuations. Confinement of angular momentum is also reduced during ECH. Studies with the TGYRO transport solver show that the model of turbulent transport embodied in the TGLF code quantitatively reproduces the measured transport in both the neutral beam (NB)-only and in the NB plus EC cases. A simple model of the decrease in toroidal rotation with EC power is set forth, which exhibits a bifurcation in the rotational state of the discharge.United States. Dept. of Energy (DE-FC02-04ER54698)United States. Dept. of Energy (DE-FC02-08ER54966)United States. Dept. of Energy (DE-AC03-09CH11466)United States. Dept. of Energy (DE-FG02-04ER54235)United States. Dept. of Energy (DE-FG0289ER53296)United States. Dept. of Energy (DE-FG02-08ER54999)United States. Dept. of Energy (DE-FG02-08ER54984)United States. Dept. of Energy (DE-FG02-04ER54461

Energetic ion transport by microturbulence is insignificant in tokamaks

Energetic ion transport due to microturbulence is investigated in magnetohydrodynamic-quiescent plasmas by way of neutral beam injection in the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)]. A range of on-axis and off-axis beam injection scenarios are employed to vary relevant parameters such as the character of the background microturbulence and the value of Eb/Te , where Eb is the energetic ion energy and Te the electron temperature. In all cases, it is found that any transport enhancement due to microturbulence is too small to observe experimentally. These transport effects are modeled using numerical and analytic expectations that calculate the energetic ion diffusivity due to microturbulence. It is determined that energetic ion transport due to coherent fluctuations (e.g., Alfvén eigenmodes) is a considerably larger effect and should therefore be considered more important for ITER.United States. Dept. of Energy (DE-FC02-04ER54698)United States. Dept. of Energy (DE-FC02-99ER54512)United States. Dept. of Energy (DE-FG03-97ER54415)United States. Dept. of Energy (DE-FG02-07ER54917)United States. Dept. of Energy (DE-AC02-09CH11466)United States. Dept. of Energy (SC-G903402)United States. Dept. of Energy (DE-FG02-08ER54984)United States. Dept. of Energy ( DE-AC52-07NA27344)United States. Dept. of Energy ( DE-FG02-89ER53296)United States. Dept. of Energy (DE-FG02-08ER54999)United States. Dept. of Energy (DE-AC05-00OR22725

Pedestal bifurcation and resonant field penetration at the threshold of edge-localized mode suppression in the DIII-D tokamak

Rapid bifurcations in the plasma response to slowly varying n=2 magnetic fields are observed as the plasma transitions into and out of edge-localized mode (ELM) suppression. The rapid transition to ELM suppression is characterized by an increase in the toroidal rotation and a reduction in the electron pressure gradient at the top of the pedestal that reduces the perpendicular electron flow there to near zero. These events occur simultaneously with an increase in the inner-wall magnetic response. These observations are consistent with strong resonant field penetration of n=2 fields at the onset of ELM suppression, based on extended MHD simulations using measured plasma profiles. Spontaneous transitions into (and out of) ELM suppression with a static applied n=2 field indicate competing mechanisms of screening and penetration of resonant fields near threshold conditions. Magnetic measurements reveal evidence for the unlocking and rotation of tearinglike structures as the plasma transitions out of ELM suppression.This work is supported by the U.S. Department of Energy under Awards No. DE-FC02-04ER54698, No. DE-AC02-09CH11466, No. DE-FG02-07ER54917, No. DE-FG02-89ER53296, No. DE-FG02-08ER54999, No. DE-FG02-08ER54984, No. DE-AC05-00OR22725, No. DE-FG02-86ER53218, and No. DE-FG02- 92ER54139