Development of sampling methods for Raman analysis of solid dosage forms of therapeutic and illicit drugs

The results of a study aimed at determining the most important experimental parameters for automated, quantitative analysis of solid dosage form pharmaceuticals (seized and model 'ecstasy' tablets) are reported. Data obtained with a macro-Raman spectrometer were complemented by micro-Raman measurements, which gave information on particle size and provided excellent data for developing statistical models of the sampling errors associated with collecting data as a series of grid points on the tablets' surface. Spectra recorded at single points on the surface of seized MDMA-caffeine-lactose tablets with a Raman microscope (lambda(ex) = 785 nm, 3 mum diameter spot) were typically dominated by one or other of the three components, consistent with Raman mapping data which showed the drug and caffeine microcrystals were ca 40 mum in diameter. Spectra collected with a microscope from eight points on a 200 mum grid were combined and in the resultant spectra the average value of the Raman band intensity ratio used to quantify the MDMA: caffeine ratio, mu(r), was 1.19 with an unacceptably high standard deviation, sigma(r), of 1.20. In contrast, with a conventional macro-Raman system (150 mum spot diameter), combined eight grid point data gave mu(r) = 1.47 with sigma(r) = 0.16. A simple statistical model which could be used to predict sigma(r) under the various conditions used was developed. The model showed that the decrease in sigma(r) on moving to a 150 mum spot was too large to be due entirely to the increased spot diameter but was consistent with the increased sampling volume that arose from a combination of the larger spot size and depth of focus in the macroscopic system. With the macro-Raman system, combining 64 grid points (0.5 mm spacing and 1-2 s accumulation per point) to give a single averaged spectrum for a tablet was found to be a practical balance between minimizing sampling errors and keeping overhead times at an acceptable level. The effectiveness of this sampling strategy was also tested by quantitative analysis of a set of model ecstasy tablets prepared from MDEA-sorbitol (0-30% by mass MDEA). A simple univariate calibration model of averaged 64 point data had R-2 = 0.998 and an r.m.s. standard error of prediction of 1.1% whereas data obtained by sampling just four points on the same tablet showed deviations from the calibration of up to 5%.

Isotopic composition of tropospheric and soil N2O from successive depths of agricultural plots with contrasting crops and nitrogen amendments

Agricultural soils are the dominant contributor to increases in atmospheric nitrous oxide (N2O). Few studies have investigated the natural N and O isotopic composition of soil N2O. We collected soil gas samples using horizontal sampling tubes installed at successive depths under five contrasting agricultural crops (e.g., unamended alfalfa, fertilized cereal), and tropospheric air samples. Mean d 15N and d 18O values of soil N2O ranged from -28.0 to +8.9‰, and from +29.0 to +53.6‰. The mean d 15N and d 18O values of tropospheric N2O were +4.6 ± 0.7‰ and +48.3 ± 0.2‰, respectively. In general, d values were lowest at depth, they were negatively correlated to soil [N2O], and d 15N was positively correlated to d 18O for every treatment on all sampling dates. N2O from the different agricultural treatments had distinct d 15N and d 18O values that varied among sampling dates. Fertilized treatments had soil N2O with low d values, but the unamended alfalfa yielded N2O with the lowest d values. Diffusion was not the predominant process controlling N2O concentration profiles. Based on isotopic and concentration data, it appears that soil N2O was consumed, as it moved from deeper to shallower soil layers. To better assess the main process(es) controlling N2O within a soil profile, we propose a conceptual model that integrates data on net N2O production or consumption and isotopic data. The direct local impact of agricultural N2O on the isotopic composition of tropospheric N2O was recorded by a shift toward lower d values of locally measured tropospheric N2O on a day with very high soil N2O emissions.

Netwar Geopolitics: Security, Failed States and Illicit Flows

Recent and emerging security policies and practices claim a mutual vulnerability that closely links human insecurity in failed states with the threat to powerful states from illicit flows. This article first examines this ‘emerging orthodoxy’ of transnational security issues that reinforces the securitisation of poverty and the poor. It then subjects this orthodoxy to theoretical and empirical critique. Theoretically it shows that this orthodoxy is formed as a ‘geopolitical imagination’ that associates and stabilises particular views of weak states and illicit flows in a ‘netwar imagination’ by reasserting and reconfiguring traditional assumptions of the spatiality and nature of threats. A final empirical section, focusing on drug production and nuclear smuggling, argues that those assumptions and their assemblage are a partial, incomplete and often self-referential reading of illicit flows.

Use of NMR metabolomic plasma profiling methodologies to identify illicit growth-promoting administrations

Detection of growth-promoter use in animal production systems still proves to be an analytical challenge despite years of activity in the field. This study reports on the capability of NMR metabolomic profiling techniques to discriminate between plasma samples obtained from cattle treated with different groups of growth-promoting hormones (dexamethasone, prednisolone, oestradiol) based on recorded metabolite profiles. Two methods of NMR analysis were investigated—a Carr–Purcell–Meiboom–Gill (CPMG)-pulse sequence technique and a conventional 1H NMR method using pre-extracted plasma. Using the CPMG method, 17 distinct metabolites could be identified from the spectra. 1H NMR analysis of extracted plasma facilitated identification of 23 metabolites—six more than the alternative method and all within the aromatic region. Multivariate statistical analysis of acquired data from both forms of NMR analysis separated the plasma metabolite profiles into distinct sample cluster sets representative of the different animal study groups. Samples from both sets of corticosteroid-treated animals—dexamethasone and prednisolone—were found to be clustered relatively closely and had similar alterations to identified metabolite panels. Distinctive metabolite profiles, different from those observed within plasma from corticosteroid-treated animal plasma, were observed in oestradiol-treated animals and samples from these animals formed a cluster spatially isolated from control animal plasma samples. These findings suggest the potential use of NMR methodologies of plasma metabolite analysis as a high-throughput screening technique to aid detection of growth promoter use.

Arsenic behaviour from groundwater and soil to crops:impacts on agriculture and food safety

High levels of As in groundwater commonly found in Bangladesh and other parts of Asia not only pose a risk via drinking water consumption but also a risk in agricultural sustainability and food safety. This review attempts to provide an overview of current knowledge and gaps related to the assessment and management of these risks, including the behaviour of As in the soil-plant system, uptake, phytotoxicity, As speciation in foods, dietary habits, and human health risks. Special emphasis has been given to the situation in Bangladesh, where groundwater via shallow tube wells is the most important source of irrigation water in the dry season. Within the soil-plant system, there is a distinct difference in behaviour of As under flooded conditions, where arsenite (AsIII) predominates, and under nonflooded conditions, where arsenate (AsV) predominates. The former is regarded as most toxic to humans and plants. Limited data indicate that As-contaminated irrigation water can result in a slow buildup of As in the topsoil. In some cases the buildup is reflected by the As levels in crops, in others not. It is not yet possible to predict As uptake and toxicity in plants based on soil parameters. It is unknown under what conditions and in what time frame As is building up in the soil. Representative phytotoxicity data necessary to evaluate current and future soil concentrations are not yet available. Although there are no indications that crop production is currently inhibited by As, long-term risks are clearly present. Therefore, with concurrent assessments of the risks, management options to further prevent As accumulation in the topsoil should already have been explored. With regard to human health, data on As speciation in foods in combination with food consumption data are needed to assess dietary exposure, and these data should include spatial and seasonal variability. It is important to control confounding factors in assessing the risks. In a country where malnutrition is prevalent, levels of inorganic As in foods should be balanced against the nutritional value of the foods. Regarding agriculture, As is only one of the many factors that may pose a risk to the sustainability of crop production. Other risk factors such as nutrient depletion and loss of organic matter also must be taken into account to set priorities in terms of research, management, and overall strategy.

TEENAGERS AND ILLICIT DRUG-USE - EXPANDING THE USER VS NONUSER DICHOTOMY

The present study examines proximal and distal factors associated with the use and non-use of illegal substances within a sample of 860 teenagers in North Wales. Arguing that there is predictive utility in expanding the traditional 'users vs non-users' design dichotomy, four groups are identified-resistant and vulnerable non-users and experimental and repeated users. 'Person' variables (life satisfaction, deviance, hopelessness and drug-related attributions) appeared to primarily differentiate the vulnerable group from their resistant counterparts and identify this, as yet non-using group, with user samples. It is suggested that these variables might represent 'risk' factors for illicit substance use and that the group design employed suggests they precede, rather than follow as a consequence of, illicit drug use. Like their resistant counterparts however, the vulnerable group are differentiated from user samples on some lifestyle and context indices. It is argued that these represent 'protective' influences in an otherwise at-risk group of non-users. Variables associated with an escalation of illicit drug use are discussed in considering the differences between the experimental and repeated user groups. Apart from the more proximal factor of drug-related attributions, 'person' variables appeared less involved here. Repeated users did however, tend to use a greater number of drugs, have a greater proportion of friends who also used illegal substances and significantly fewer had a Welsh cultural identity.

Response of farmland biodiversity to the introduction of bioenergy crops: effects of local factors and surrounding landscape context

The recent growth in bioenergy crop cultivation, stimulated by the need to implement measures to reduce net CO emissions, is driving major land-use changes with consequences for biodiversity and ecosystem service provision. Although the type of bioenergy crop and its associated management is likely to affect biodiversity at the local (field) scale, landscape context and its interaction with crop type may also influence biodiversity on farms. In this study, we assessed the impact of replacing conventional agricultural crops with two model bioenergy crops (either oilseed rape Brassica napus or Miscanthus × giganteus) on vascular plant, bumblebee, solitary bee, hoverfly and carabid beetle richness, diversity and abundance in 50 sites in Ireland. We assessed whether within-field biodiversity was also related to surrounding landscape structure. We found that local- and landscape-scale variables correlated with biodiversity in these agricultural landscapes. Overall, the differences between the bioenergy crops and the conventional crops on farmland biodiversity were mostly positive (e.g. higher vascular plant richness in Miscanthus planted on former conventional tillage, higher solitary bee abundance and richness in Miscanthus and oilseed rape compared with conventional crops) or neutral (e.g. no differences between crop types for hoverflies and bumblebees). We showed that these crop type effects were independent of (i.e. no interactions with) the surrounding landscape composition and configuration. However, surrounding landscape context did relate to biodiversity in these farms, negatively for carabid beetles and positively for hoverflies. Although we conclude that the bioenergy crops compared favourably with conventional crops in terms of biodiversity of the taxa studied at the field scale, the effects of large-scale planting in these landscapes could result in very different impacts. Maintaining ecosystem functioning and the delivery of ecosystem services will require a greater understanding of impacts at the landscape scale to ensure the sustainable development of climate change mitigation measures.

Political Posturing or Real Powers: Control of Genetically Modified Crops by the Member States and their Regions

The cultivation of genetically modified (GM) crops in the EU is highly harmonised, involving a central authorisation procedure that aims to ensure a high level of environmental and human health protection. However conflicts over authority persist and the Commission has responded to a combination of internal and external pressures with a more flexible approach to coexistence, a proposed opt-out clause and recently a promise by the head of the Commission to review the existing EU GM legislative regime, providing an opportunity to consider and suggest paths of development. In light of the significance of multilevel governance and subsidiarity for GM cultivation, this paper considers the policy-making powers of the Member States and subnational regions in this regime, focussing upon post-authorisation options in particular. A number of core mechanisms exist, including voluntary measures, safeguard clauses, coexistence measures, a proposed express opt-out and Article 4(2) TEU on ‘national identity. These mechanisms are examined in light of the goals and challenges of multilevel governance, in order to consider whether the relevant powers are located at the appropriate level. Overall, it is apparent that the developments occurring at the EU level are strengthening multilevel governance, but with significant opportunities to improve it further through focussing on the supporting roles and the regional levels in particular.