An attempt was made to evaluate the importance of smoke and toxic gas inhalation in fires by comparing the volatile constituents in blood taken from fire fatalities with those of normal healthy and post-mortem controls. At the initial stage of the project, particular attention was given to the measurement of carbonyl compounds which represent a series of toxic and strongly irritant thermal degradation products from many polymeric materials. Three analytical methods, namely, i) gas chromatographic analysis of carbonyls after conversion to their corresponding 2,4-dinitrophenyl hydrazone derivatives, ii) direct static headspace gas chromatography, and iii) dynamic headspace gas chromatography, were compared for their applicability to the measurement of carbonyls in blood. Problems associated with binding of carbonyls to blood proteins were experienced in the first two methods which precluded their use for this application. The latter method was found to be most suitable in this respect since the bound carbonyls were released during the purging process. The method was also the most sensitive and when used in conjunction with a mass spectrometer, a detection limit in the nanogram per millilitre range was obtained. Volatiles in blood were extracted by purging the samples (1 ml) with 0.6 litre of helium and collecting the components on a small Tenax-GC column. The volatiles were then thermally desorbed and analysed by gas chromatography-mass spectrometry using a 100 m x 0.5 mm i.d. Carbowax 20M SCOT column. The sorption technique was found to extract a wide range of volatile components from blood enabling a comparison of volatile profiles to be made. Thus initially organic nitriles as well as the carbonyl compounds were quantified. Volatile components were identified by comparison of their retention indices and mass spectra with those of authentic standards. Where the latter were not available, tentative identifications were made 9n the basis of their mass spectral data only. Quantification of carbonyls and nitriles was achieved by comparing their response ratios to those from an external standard under identical conditions. During the period from August 1981 to May 1982, thirty-one blood volatile profiles were studied. These included four normal healthy controls and six post-mortem controls. In general, more complex profiles were found in fire fatalities than those of the controls. Over 140 chemical species have been identified in these! profiles and these include series of carbonyls, nitriles, alcohols, esters, aliphatic and aromatic hydrocarbons, halogenated hydrocarbons, heterocyclic compounds and sulphur-containing compounds. A detailed examination of the profiles has indicated that those compounds which might be of significance fell into two main catagories: those which were strong sensory and respiratory irritants, and those which were depressants of the central nervous system. Quantitative measurements of carbonyls in blood have shown that the mean levels of 2-butanone, butandione, 2-pentanone, cyclopentanone, cyclohexanone and hexanal were higher in fire fatalities than those in the controls. Of particular concern were the very high levels of acetonitrile and the presence of acrolein Ca highly toxic and strong sensory irritant) in the blood of some of the fire fatalities. Although the toxicological significance of these gaseous toxicants in causing fire fatalities has yet to be established, the results have clearly demonstrated that most of the fire deaths included in this exposed to a wide range of toxicants. these compounds may have played a vital incapacitation during the fire.

Mitochondrial DNA analysis was undertaken on samples collected from two populations in Peninsular Malaysia, the Modern Malay (102 samples) and Orang Asli (59 samples from Jahai and Kinsiu sub-groups). The hypervariable region 1 (HV1) of the mtDNA control region was amplified and sequenced. Polymorphisms were reported by aligning each sequence to the Cambridge Reference Sequence (CRS). A total of 94 polymorphisms were observed in the Modern Malay samples, which formed 75 different haplotypes. The Orang Asli showed notably lower number of the HV1 region variations, with only 28 polymorphisms and 13 haplotypes observed. Genetic diversity calculated for the Modern Malays and Orang Asli were 0.989 and 0.818, respectively. Probability of random match calculated was 0.0202 for the Modern Malays and 0.1962 for the Orang Asli. The mtDNA coding region variations was examined using RFLP analysis. Combination of both RFLP and HV1 sequence data had placed the Modern Malays into three major Southeast Asian haplogroups, M, B and F. These findings had initially suggested that the Modern Malays shared a common lineage with other populations within this region. Two novel sub-clusters, M21a and R21 were found at a high frequency within the Orang Asli samples. These sub-clusters, which have also been found in other Semang sub-groups appear to be indigenous Semang haplogroups. The limited number of mtDNA haplotypes shared between the Modern Malays and Orang Asli suggested discontinuity of mtDNA between these populations. Even though both populations were believed to be among the earliest populations of Peninsular Malaysia, this result indicates that the Modern Malays were not direct descendants of the Orang Asli. Minisequencing analysis was carried for further interrogation of the mtDNA coding region polymorphisms. Besides mtDNA analysis, the autosomal STR markers were also examined using PowerPlex® 16 system for both populations. These data could provide more information when added to the available STR database for Malaysian populations.

This thesis examines the use of bile and nail as alternative biological specimens in forensic toxicology. In chapter 1, a brief overview of the mechanisms of substance passage into and out of membranes and fluids and matrices was presented followed by a review of the use of alternative biological specimens for analytical purposes. The experimental part of this thesis begins in chapter 2 where a simple and rapid method for the detection and quantification of dextropropoxyphene in bile and its major metabolite, norpropoxyphene, is presented. Following this, nail is examined as an alternative biological specimen in cases of medico-legal interest. Firstly, two major cannabinoids, 9-tetrahydrocannabinol and 11-nor-9-tetrahydrocannabinol-9-carboxylic acid were identified in the nail (chapter 3) by means of RIA and GC-MS. Cannabinoids were found to be present in all six cases that were analysed for cannabinoids by RIA and their concentration ranged from 0.23 ng/mg to 2.80 ng/mg (average: 1.03 ng/mg). Using GC-MS, 9-tetrahydrocannabinol was detected in 11 out of the 14 nail clipping hydrolysates after basic extraction with concentrations ranging from 0.13 ng/mg to 6.97 ng/mg (average: 1.44 ng/mg). 11-nor-9-tetrahydrocannabinol-9-carboxylic acid was not detected in any of these nail clipping hydrolysates but was detected in two of the three fingernail clipping hydrolysates extracted under acidic pH with concentrations ranging from 9.82 ng/mg to 29.7 ng/mg (average: 19.8 ng/mg). In chapter 4, the detection and quantification of diazepam, the most commonly encountered benzodiazepine, were described. Using ECD-GC, diazepam was detected in hydrolysates of all 6 sets of nail clippings in concentrations ranging from 4.37 to 87.8 ng/mg (average: 25.7 ng/mg). In chapter 5, an analytical protocol for the detection and quantification of morphine in nail clippings of known heroin abusers was presented. Finally, a protocol for the detection and quantification of methadone in nail clippings of patients attending a methadone maintenance program was presented.

Experimental mixed-mode solid-phase extraction columns of differing carbon number and carbon loading were investigated for the efficient extraction of drugs of abuse from biological matrices. Methadone and its two major metabolites (EDDP and EMDP) were chosen due to the increase in methadone drug-related deaths in the West of Scotland. Amphetamine and related compounds (methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methyleneidoxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA)) were chosen because of the prevalence of use of "speed" and "ecstasy" throughout the United Kingdom and the challenge these volatile drugs pose to the analyst. Improved methods were developed for the efficient extraction of methadone, EDDP and EMDP from whole blood and for amphetamine and related compounds from whole blood and hair. These methods were successfully applied to the analysis of postmortem samples. The stability of methadone, EDDP and EMDP in whole blood was investigated using the developed extraction method after sorting at various temperatures for a period of six months. Methadone remained stable in blood after six months. This was confirmed by the analysis of postmortem cases samples which when re-analysed within six months of the initial analysis, correlated well. Postmortem hair samples proved useful for determining antecedent drug use history whether extracted by solid-phase extraction or after screening with a Cohort enzyme immunoassay kit, adapted for hair analysis. Solid-phase extraction provides a clean and efficient means of extracting drugs of abuse from whole blood and hair. Simple manipulation of the extraction system (sample pretreatment, pH, derivatisation) provides a versatile alternative to lengthy liquid-liquid extraction techniques and has the added potential of automation.

The use of supercritical fluid extraction (SFE) was evaluated for the determination of drugs of Forensic interest. Three matrices were investigated. The first two (blood and vitreous humor) were compared to SPE and LLE methodology currently in use at the Department of Forensic Science and Medicine. The third matrix, hair, was assessed to determine its usefulness as a marker of past drug use. Three types of drugs were investigated by SFE namely, Benzodiazepines, morphine and methadone. Successful methodology was developed for all three matrices and all three drug types, providing an efficient, reproducible alternative method to SPE and LLE, which reduced the environmental risks from organic solvents. The developed methods were applied to the analysis of authentic forensic samples. In addition to comparing well with the results obtained with the conventional techniques, good correlation was obtained between blood and vitreous humor results for temazepam, diazepam, methadone and morphine. Thus, in cases where a body is badly decomposed or burned, vitreous humor can be used as an alternative post-mortem sample. In addition to the determination of morphine, 6-monoacetyl morphine (6MAM) was used as marker of heroin abuse. 6MAM was detected in all three samples matrices, thus confirming the use of heroin prior to death. Hair analysis for all three types of drugs was carried out using a single extraction method. A wide range of concentrations was found for all drug types. As with blood and vitreous humor, 6MAM was detected and used as a marker of heroin abuse. From this, 61% of known heroin users were confirmed.

The work described in this thesis was in the field of Forensic Toxicology, which is the study and practice of toxicology for legal purposes. Three different application areas were considered: (a) the analysis of drugs in blood by gas chromatography-mass spectrometry (GC-MS) following isolation from the biological matrix by solid phase extraction procedures, (b) the analysis of paint solvents in blood by gas chromatography (GC) and GC-MS following dynamic headspace elution from blood, and (c) an evaluation of Thermospray/Plasmaspray (TSP/PSP LC-MS) liquid chromatography-mass spectrometry as the basis of drug screening techniques in forensic toxicology. (a) In the first of these areas, a sensitive, specific and reliable method was developed for the analysis of basic drugs in blood, using morphine and buprenorphine as model compounds which are also drugs commonly abused in the Glasgow area. A novel extraction procedure was used, based on a commercially available chemically-modified silica containing surface-bound benzenesulphonylpropyl groups, which served as a cation exchange resin. Several methods for the initial treatment of the biological matrix wre examined and the one selected involved absorption of the blood sample on diatomaceous earth and solvent elution of the crude extract containing any drugs present in the sample. This extract was then purified using the cation exchange resin: conditions suitable for the efficient retention of basic drugs and subsequent elution were also examined and developed. The extraction efficiencies for morphine were 925% and 954% at concentrations of 35 and 560ng/ml blood, respectively, for buprenorphine 836% and 875% , at concentration of 0.5 and 8ng/ml respectively, and for other drugs were better than 85% . The end-step analytical technique chosen for this method was GC-MS, because of analytical and legal requirements with respect to sensitivity and specificity. The polar nature of the model compounds, and of many other drugs likely to be encountered in this field, required chemical modification of the substances prior to gas chromatography. A comparison was made of three silyl ether derivatives - the trimethylsily (TMS), ethyldimethylsilyl (EMS) and tert-butyldimethylsilyl (MTBS) ethers. The conditions required for derivative formation were examined, including the choice of silyl donor reagent, solvents, temperature of reaction and time to completion. The EDMS donor, diethyltetramethyldisilazane, was selected on the basis of the midl reaction conditions required for the test compounds and also because this reagent caused less interference during GC-MS analysis. EDMS ethers gave satisfactory gas chromatographic behaviour and the presence of prominent ions at high mass was shown to be advantageous for specific and sensitive detection by SIR-MS with little background interference. The developed method was considered to be useful for both clinical and post-mortem blood samples containing morphine and buprenorphine down to the low picogram/millilitre level, and therefore adequate for the intended purpose. The method was subsequently applied to 13 samples submitted for analysis to the Department of Forensic Medicine and Science and found to be satisfactory. (b) In the second area of application, dynamic head space (DHS) elution was used for the analysis of paint solvents in blood. Volatilised solvents were trapped on a Tenax-GC cartridge and were subsequently analysed by GC-MS. The extraction efficiency of this method for C18-C12 n-alkane hydrocarbons, which were present in the paint materials, was better than 90% and sensitivity down to pg/ml levels was obtained. Solvent extraction procedures for these hydrocarbons were evaluated using high purity solvent. The extraction efficiency was better than 85% . Analysis of extracts by GC or GC-MS suffered from interference from the solvent front which reduced the sensitivity. The DHS method was applied to a pilot study for occupational monitoring of a group of painters to assess the presence of paint solvents in their blood. Two venous blood samples were collected at the beginning and at the end of a working week from each subject. They showed the presence of several solvents similar to those present in paint material and the levels in the second series of samples were higher than those of the first series. The differences between the levels in the two series were statistically significant for n-nonane, n-undecane and alkylbenzenes. The levels in the first sample indicated incomplete clearance of these solvents from the body during the weekend, and the second samples indicated solvent uptake during the working week. Solvent contamination in the extraction system was tackled by several approaches but still hindered the accurate estimation of solvent levels in blood. (c) In the third area of application, the operating parameters which control the sensitivity of the mass spectrometer using the TSP/PSP LC-MS interface were evaluated. These included the effects of the probe temperature and discharge voltage on sensitivity and mass spectral fragmentation pattern and the effects of the mobile phase constituents on sensitivity and mass spectral peak stability. Solvent systems containing ammonium acetate buffer and an organic modifier such as acetonitrile produced the best results in plasmaspray LC-MS. Three model HPLC-MS analyses were developed for mixtures of basic drugs, barbiturates and opiates using both the plasmaspray positive and negative ion modes. During the development of the mobile phases, the optimization of chromatography by organic modifiers was assessed. The quality of chromatography obtained was not always as good as expected in conventional HPLC, but the combination of chromatographic and mass spectral data could be used for identification and quantification purposes. A compilation of PSP mass spectra of drugs commonly encountered in forensic toxicology was produced. These mass spectra provided mostly molecular weight information with little structural information.

Exploring and understanding the practice of accurately assessing offenders is an important area of research for forensic practice and the risk management of offenders. This thesis aims to explore different approaches to offender assessment, specifically their clinical utility in forensic mental health settings. The first chapter, provides an introduction to the importance of accurate offender assessment, and presents current models proposed within the literature. The second chapter, provides a systematic review of historically used approaches in the assessment of risk, and compares their predictive accuracy and clinical utility in relation to a mentally disordered offending population. The third chapter, critically appraises a widely used assessment tool to assess risk within forensic mental health settings, the HCR-20 (Version 3.0; Douglas, Hart, Webster & Belfrage, 2013). The fourth chapter, moves way from specific tools used in current practice and instead explores clinicians current understanding and use of newer concepts in offender assessment (IOW/IOA), through a qualitative research study. Finally, the fifth chapter presents a thorough discussion of the overall content, findings and conclusions of this thesis. Findings have important implications for the practice of assessing and managing offenders effectively.

A systematic literature review summarizes what is known about the relationships between attachment, relational security and therapeutic relationships. A paucity of research with forensic populations is noted. Consequently the empirical research paper explores more systematically the relationships between these variables on forensic psychiatric wards. Suggestions for staff and service development are presented. No relationships were found between relational security and service users’ attachment to the service and between relational security and risk events and treatment outcomes. Additional analyses revealed that relational security and ward atmosphere were moderately correlated. A large positive correlation was found between patients’ attachment to the service and ward atmosphere, and a moderate, negative, relationship was found between patients’ attachment to the service and risk incidents Multiple regression revealed that relational security and ward atmosphere significantly predicted patients’ attachment to the service. More robust research is needed to investigate the relationships between attachment, relational security, risk incidents and treatment outcomes on forensic psychiatric wards. An argument is made for promoting stronger therapeutic relationships between staff and service users so that forensic wards can become closer to secure bases which might help clients to overcome past interpersonal traumas and develop safer ways to relate interpersonally.

In forensic investigations involving severely burned human remains, dental analysis stands alone as other means of identification are often destroyed. Therefore, the aim of the present work was to investigate the influence of duration of heat exposure and heating regimes regarding the macroscopic, compositional, structural and crystalline alterations of dental tissues. Experiments were carried out using 215 freshly extracted human teeth, exposed to temperatures of 400 to 1000°C. Shrinkage and shape preservation was analysed using micro-CT, whilst crystalline alterations were evaluated with synchrotron-based SAXS/WAXS experiments. The alterations of organic constituents were assessed using TGA and FTIR. Moreover, calibrated digital photographs were used to document and analyse colour alterations. Although dentinal shrinkage was found at 400°C, tooth morphology was well preserved even at 1000°C. Surface colour alterations were linked to the degradation of organic components, and were highly dependent upon the duration of heat exposure and the heating regime, whilst crystalline alterations were less influenced by these factors. The combination of novel analytical approaches enabled the documentation and quantification of heat-induced alterations of dental tissues, providing results that can be used in the forensic identification process and allow an improved estimation of the cremation temperature range based on human dental remains.

Translation of author's diss., Quaestio medico-chirurgica ... An mortis incertae signa; original Latin text p. [11]-40. / Also available online.