National and Regional Estimates of the Prevalence of Opiate and/or Crack Cocaine use 2008-09: A summary of key findings

<p>This report summarises the results of a follow-up study to a three year project to estimate the prevalence of ‘problem drug use’ (defined as use of opiates and/or crack cocaine) nationally (England only), regionally and locally. The follow-up was carried out two years after the final sweep of the original project, so could therefore be considered as ‘sweep 5’. An overview of the national and regional estimates are presented in this report, as are comparisons with the estimates produced by the third (2006-07) sweep of the study. Estimates for 2007-08 are not available as a study was not commissioned for that year.</p> <p>Information about the number of people who use illicit drugs such as heroin, other opiates or crack cocaine is key to formulating effective policies for tackling drug-related harm as these drugs are associated with the highest levels of harm. It also helps inform service provision at the local level and provides a context in which to understand the population impact of interventions to reduce drug-related harm.</p> <p>Direct enumeration of those engaged in a largely covert activity such as the use of class A drugs is difficult and standard household survey techniques tend to underestimate the extent of such activity. Indirect techniques making use of various data sources offer a more reliable way of calculating prevalence estimates for the use of opiates and/or crack cocaine. The estimates presented in this report are derived using two indirect measurement techniques: the capture-recapture method (CRC ); and the multiple indicator (MIM ) method. These methods are described in detail in Hay et al., 2006 and Hay et al., 2007a. Methodological developments throughout the course of the previous three sweeps are discussed elsewhere (Hay et al., 2007b, Hay et al., 2008). The individuals covered by this study were people aged 15 to 64 and resident in each DAT area, and known to be using heroin, methadone, other opiate drugs or crack cocaine.</p&gt

Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals were administered via the drinking water or concentrations of 10-1000 micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100 micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/l), which is a weak estrogen or nonestrogenic in vitro, were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tap water. In study 1, rats were treated from days 1-22 after births in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating throughout gestation and 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect or body weight: in most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OP, OPP, or BBP at a concentration of 1000 micrograms/1 resulted in a small (5-13%) but significant (p < 0.01 or p < 0.0001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body, weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OP. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the spermatogenic cycle, but DES, OP, and BBP caused reductions of 10-21% (p < 0.05 to p < 0.001) in daily sperm production. Humans are exposed to phthalates, such as BBP, and to alkylphenol polyethoxylates, such as OP, but to what extent is unknown. More detailed studies are warranted to assess the possible risk to the development of the human testis from exposure to these and other environmental estrogens

Galactic Edge Clouds I: Molecular Line Observations and Chemical Modelling of Edge Cloud 2

Edge Cloud 2 (EC2) is a molecular cloud, about 35 pc in size, with one of the largest galactocentric distances known to exist in the Milky Way. We present observations of a peak CO emission region in the cloud and use these to determine its physical characteristics. We calculate a gas temperature of 20 K and a density of n(H2) ~ 10^4 cm^-3. Based on our CO maps, we estimate the mass of EC2 at around 10^4 M_sun and continuum observations suggest a dust-to-gas mass ratio as low as 0.001. Chemical models have been developed to reproduce the abundances in EC2 and they indicate that: heavy element abundances may be reduced by a factor of five relative to the solar neighbourhood (similar to dwarf irregular galaxies and damped Lyman alpha systems); very low extinction (Av < 4 mag) due to a very low dust-to-gas ratio; an enhanced cosmic ray ionisation rate; and a higher UV field compared to local interstellar values. The reduced abundances may be attributed to the low level of star formation in this region and are probably also related to the continuing infall of primordial (or low metallicity) halo gas since the Milky Way formed. Finally, we note that shocks from the old supernova remnant GSH 138-01-94 may have determined the morphology and dynamics of EC2.Comment: Accepted by ApJ 7 August 2007. 29 pages, 9 figures, 10 tables. PMR now at NRAO, Green Bank, WV, USA. TJM now at Queen's University Belfast, UK. GB now at Yale University, CT, US

MicroR159 regulation of most conserved targets in Arabidopsis has negligible phenotypic effects

BACKGROUND A current challenge of microRNA (miRNA) research is the identification of biologically relevant miRNA:target gene relationships. In plants, high miRNA:target gene complementarity has enabled accurate target predictions, and slicing of target mRNAs has facilitated target validation through rapid amplification of 5' cDNA ends (5'-RACE) analysis. Together, these approaches have identified more than 20 targets potentially regulated by the deeply conserved miR159 family in Arabidopsis, including eight MYB genes with highly conserved miR159 target sites. However, genetic analysis has revealed the functional specificity of the major family members, miR159a and miR159b is limited to only two targets, MYB33 and MYB65. Here, we examine the functional role of miR159 regulation for the other potential MYB target genes. RESULTS For these target genes, functional analysis failed to identify miR159 regulation that resulted in any major phenotypic impact, either at the morphological or molecular level. This appears to be mainly due to the quiescent nature of the remaining family member, MIR159c. Although its expression overlaps in a temporal and spatial cell-specific manner with a subset of these targets in anthers, the abundance of miR159c is extremely low and concomitantly a mir159c mutant displays no anther defects. Examination of potential miR159c targets with conserved miR159 binding sites found neither their spatial or temporal expression domains appeared miR159 regulated, despite the detection of miR159-guided cleavage products by 5'-RACE. Moreover, expression of a miR159-resistant target (mMYB101) resulted predominantly in plants that are indistinguishable from wild type. Plants that displayed altered morphological phenotypes were found to be ectopically expressing the mMYB101 transgene, and hence were misrepresentative of the in vivo functional role of miR159. CONCLUSIONS This study presents a novel explanation for a paradox common to plant and animal miRNA systems, where among many potential miRNA-target relationships usually only a few appear physiologically relevant. The identification of a quiescent miR159c:target gene regulatory module in anthers provides a likely rationale for the presence of conserved miR159 binding sites in many targets for which miR159 regulation has no obvious functional role. Remnants from the demise of such modules may lead to an overestimation of miRNA regulatory complexity when investigated using bioinformatic, 5'-RACE or transgenic approaches.RSA was funded by an ANU postgraduate scholarship and by a CSIRO Emerging Science Initiative. JL is the recipient of an ANU international student postgraduate scholarship. This research was supported by an Australian Research Council grant DP0773270

Parameter inference in mechanistic models of cellular regulation and signalling pathways using gradient matching

A challenging problem in systems biology is parameter inference in mechanistic models of signalling pathways. In the present article, we investigate an approach based on gradient matching and nonparametric Bayesian modelling with Gaussian processes. We evaluate the method on two biological systems, related to the regulation of PIF4/5 in Arabidopsis thaliana, and the JAK/STAT signal transduction pathway

The fundamental problem of command : plan and compliance in a partially centralised economy

When a principal gives an order to an agent and advances resources for its implementation, the temptations for the agent to shirk or steal from the principal rather than comply constitute the fundamental problem of command. Historically, partially centralised command economies enforced compliance in various ways, assisted by nesting the fundamental problem of exchange within that of command. The Soviet economy provides some relevant data. The Soviet command system combined several enforcement mechanisms in an equilibrium that shifted as agents learned and each mechanism's comparative costs and benefits changed. When the conditions for an equilibrium disappeared, the system collapsed.Comparative Economic Studies (2005) 47, 296–314. doi:10.1057/palgrave.ces.810011

Data management of nanometre­ scale CMOS device simulations

In this paper we discuss the problems arising in managing and curating the data generated by simulations of nanometre scale CMOS (Complementary Metal–Oxide Semiconductor) transistors, circuits and systems and describe the software and operational techniques we have adopted to address them. Such simulations pose a number of challenges including, inter alia, multi­TByte data volumes, complex datasets with complex inter-relations between datasets, multi­-institutional collaborations including multiple specialisms and a mixture of academic and industrial partners, and demanding security requirements driven by commercial imperatives. This work was undertaken as part of the NanoCMOS project. However, the problems, solutions and experience seem likely to be of wider relevance, both within the CMOS design community and more generally in other disciplines