Chromatographic analysis and survey studies to evaluate the emerging drugs of synthetic cannabinoids in Scotland and Saudi Arabia

Synthetic cannabinoid receptor agonists or more commonly known as synthetic cannabinoids (SCs) were originally created to obtain the medicinal value of THC but they are an emerging social problem. SCs are mostly produced coated on herbal materials or in powder form and marketed under a variety of brand names, e.g. “Spice”, “K2”. Despite many SCs becoming controlled under drug legislation, many of them remain legal in some countries around the world. In Scotland, SCs are controlled under the Misuse of Drugs Act 1971 and Psychoactive Substances Act 2016 that only cover a few early SCs. In Saudi Arabia, even fewer are controlled. The picture of the SCs-problem in Scotland is vague due to insufficient prevalence data, particularly that using biological samples. Whilst there is evidence of increasing use of SCs throughout the world, in Saudi Arabia, there is currently no data regarding the use of products containing SCs among Saudi people. Several studies indicate that SCs may cause serious toxicity and impairment to health therefore it is important to understand the scale of use within society. A simple and sensitive method was developed for the simultaneous analysis of 10 parent SCs (JWH-018, JWH-073, JWH-250, JWH-200, AM-1248, UR-144, A-796260, AB-FUBINACA, 5F-AKB-48 and 5F-PB-22) in whole blood and 8 corresponding metabolites (JWH-018 4-OH pentyl, JWH-073 3-OH butyl, JWH-250 4-OH pentyl, AM-2201 4-OH pentyl, JWH-122 5-OH pentyl, JWH-210 5-OH pentyl, 5F-AKB-48 (N-4 OH pentyl), 5F-PB-22 3-carboxyindole)in urine using LLE and LC-MS/MS. The method was validated according to the standard practices for method validation in forensic toxicology (SWGTOX, May 2013). All analytes gave acceptable precision, linearity and recovery for analysing blood and urine samples. The method was applied to 1,496 biological samples, a mixture of whole blood and urine. Blood and/or urine samples were analysed from 114 patients presenting at Accident and Emergency in Glasgow Royal Infirmary, in spring 2014 and JuneDecember 2015. 5F-AKB-48, 5F-PB-22 and MDMB-CHMICA were detected in 9, 7 and 9 cases respectively. 904 urine samples from individuals admitted to/liberated from Scottish prisons over November 2013 were tested for the presence of SCs. 5F-AKB-48 (N-4 OH pentyl) was detected in 10 cases and 5F-PB-22 3-carboxyindole in 3 cases. Blood and urine samples from two post-mortem cases in Scotland with suspected ingestion of SCs were analysed. Both cases were confirmed positive for 5F-AKB-48. A total of 463 urine samples were collected from personnel who presented to the Security Forces Hospital in Ryiadh for workplace drug testing as a requirement for their job during July 2014. The results of the analysis found 2 samples to be positive for 5F-PB-22 3carboxyindole. A further study in Saudi Arabia using a questionnaire was carried out among 3 subpopulations: medical professionals, members of the public in and around smoking cafes and known drug users. With regards to general awareness of Spice products, 16%, 11% and 22% of those participants of medical professionals, members of the public in and around smoking cafes and known drug users, respectively, were aware of the existence of SCs or Spice products. The respondents had an overall average of 4.5% who had a friend who used these Spice products. It is clear from the results obtained in both blood and urine testing and surveys that SCs are being used in both Scotland and Saudi Arabia. The extent of their use is not clear and the data presented here is an initial look into their prevalence. Blood and urine findings suggest changing trends in SC use, moving away from JWH and AM SCs to the newer 5F-AKB-48, 5-F-PB-22 and MDMBCHMICA compounds worldwide. In both countries 5F-PB-22 was detected. These findings clarify how the SCs phenomenon is a worldwide problem and how the information of every country regarding what SCs are seized can help and is not specific for that country. The analytes included in the method were selected due to their apparent availability in both countries, however it is possible that some newer analytes have been used and these would not have been detected. For this reason it is important that methods for testing SCs are updated regularly and evolve with the ever-changing availability of these drugs worldwide. In addition, there is little published literature regarding the concentrations of these drugs found in blood and urine samples and this work goes some way towards understanding these.

An ontology for risk management of digital collections

Maintaining accessibility to and understanding of digital information over time is a complex challenge that often requires contributions and interventions from a variety of individuals and organizations. The processes of preservation planning and evaluation are fundamentally implicit and share similar complexity. Both demand comprehensive knowledge and understanding of every aspect of to-be-preserved content and the contexts within which preservation is undertaken. Consequently, means are required for the identification, documentation and association of those properties of data, representation and management mechanisms that in combination lend value, facilitate interaction and influence the preservation process. These properties may be almost limitless in terms of diversity, but are integral to the establishment of classes of risk exposure, and the planning and deployment of appropriate preservation strategies. We explore several research objectives within the course of this thesis. Our main objective is the conception of an ontology for risk management of digital collections. Incorporated within this are our aims to survey the contexts within which preservation has been undertaken successfully, the development of an appropriate methodology for risk management, the evaluation of existing preservation evaluation approaches and metrics, the structuring of best practice knowledge and lastly the demonstration of a range of tools that utilise our findings. We describe a mixed methodology that uses interview and survey, extensive content analysis, practical case study and iterative software and ontology development. We build on a robust foundation, the development of the Digital Repository Audit Method Based on Risk Assessment. We summarise the extent of the challenge facing the digital preservation community (and by extension users and creators of digital materials from many disciplines and operational contexts) and present the case for a comprehensive and extensible knowledge base of best practice. These challenges are manifested in the scale of data growth, the increasing complexity and the increasing onus on communities with no formal training to offer assurances of data management and sustainability. These collectively imply a challenge that demands an intuitive and adaptable means of evaluating digital preservation efforts. The need for individuals and organisations to validate the legitimacy of their own efforts is particularly prioritised. We introduce our approach, based on risk management. Risk is an expression of the likelihood of a negative outcome, and an expression of the impact of such an occurrence. We describe how risk management may be considered synonymous with preservation activity, a persistent effort to negate the dangers posed to information availability, usability and sustainability. Risk can be characterised according to associated goals, activities, responsibilities and policies in terms of both their manifestation and mitigation. They have the capacity to be deconstructed into their atomic units and responsibility for their resolution delegated appropriately. We continue to describe how the manifestation of risks typically spans an entire organisational environment, and as the focus of our analysis risk safeguards against omissions that may occur when pursuing functional, departmental or role-based assessment. We discuss the importance of relating risk-factors, through the risks themselves or associated system elements. To do so will yield the preservation best-practice knowledge base that is conspicuously lacking within the international digital preservation community. We present as research outcomes an encapsulation of preservation practice (and explicitly defined best practice) as a series of case studies, in turn distilled into atomic, related information elements. We conduct our analyses in the formal evaluation of memory institutions in the UK, US and continental Europe. Furthermore we showcase a series of applications that use the fruits of this research as their intellectual foundation. Finally we document our results in a range of technical reports and conference and journal articles. We present evidence of preservation approaches and infrastructures from a series of case studies conducted in a range of international preservation environments. We then aggregate this into a linked data structure entitled PORRO, an ontology relating preservation repository, object and risk characteristics, intended to support preservation decision making and evaluation. The methodology leading to this ontology is outlined, and lessons are exposed by revisiting legacy studies and exposing the resource and associated applications to evaluation by the digital preservation community.

Eulerian-Lagrangian definition of coarse bed-load transport: Theory and verification with low-cost inertial measurement units

Fluvial sediment transport is controlled by hydraulics, sediment properties and arrangement, and flow history across a range of time scales. This physical complexity has led to ambiguous definition of the reference frame (Lagrangian or Eulerian) in which sediment transport is analysed. A general Eulerian-Lagrangian approach accounts for inertial characteristics of particles in a Lagrangian (particle fixed) frame, and for the hydrodynamics in an independent Eulerian frame. The necessary Eulerian-Lagrangian transformations are simplified under the assumption of an ideal Inertial Measurement Unit (IMU), rigidly attached at the centre of the mass of a sediment particle. Real, commercially available IMU sensors can provide high frequency data on accelerations and angular velocities (hence forces and energy) experienced by grains during entrainment and motion, if adequately customized. IMUs are subjected to significant error accu- mulation but they can be used for statistical parametrisation of an Eulerian-Lagrangian model, for coarse sediment particles and over the temporal scale of individual entrainment events. In this thesis an Eulerian-Lagrangian model is introduced and evaluated experimentally. Absolute inertial accelerations were recorded at a 4 Hz frequency from a spherical instrumented particle (111 mm diameter and 2383 kg/m3 density) in a series of entrainment threshold experiments on a fixed idealised bed. The grain-top inertial acceleration entrainment threshold was approximated at 44 and 51 mg for slopes 0.026 and 0.037 respectively. The saddle inertial acceleration entrainment threshold was at 32 and 25 mg for slopes 0.044 and 0.057 respectively. For the evaluation of the complete Eulerian-Lagrangian model two prototype sensors are presented: an idealised (spherical) with a diameter of 90 mm and an ellipsoidal with axes 100, 70 and 30 mm. Both are instrumented with a complete IMU, capable of sampling 3D inertial accelerations and 3D angular velocities at 50 Hz. After signal analysis, the results can be used to parametrize sediment movement but they do not contain positional information. The two sensors (spherical and ellipsoidal) were tested in a series of entrainment experiments, similar to the evaluation of the 111 mm prototype, for a slope of 0.02. The spherical sensor entrained at discharges of 24.8 ± 1.8 l/s while the same threshold for the ellipsoidal sensor was 45.2 ± 2.2 l/s. Kinetic energy calculations were used to quantify the particle-bed energy exchange under fluvial (discharge at 30 l/s) and non-fluvial conditions. All the experiments suggest that the effect of the inertial characteristics of coarse sediments on their motion is comparable to the effect hydrodynamic forces. The coupling of IMU sensors with advanced telemetric systems can lead to the tracking of Lagrangian particle trajectories, at a frequency and accuracy that will permit the testing of diffusion/dispersion models across the range of particle diameters.