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"Maskell, Peter D"
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Forensic science education and training : a tool-kit for lecturers and practitioner trainers
\"A comprehensive and innovative guide to teaching, learning and assessment in forensic science education and practitioner training Includes student exercises for mock crime scene and disaster scenarios Addresses innovative teaching methods including apps and e-gaming Discusses existing and proposed teaching methods\"-- Provided by publisher.
Book
The blood-to-plasma ratio and predicted GABAA-binding affinity of designer benzodiazepines
Purpose
The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the blood-to-plasma ratio. Knowledge of the pharmacodynamics of designer benzodiazepines is also important, and the use of quantitative structure–activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABA
A
receptor.
Methods
In this work, the blood-to-plasma ratios for six designer benzodiazepines (deschloroetizolam, diclazepam, etizolam, meclonazepam, phenazepam, and pyrazolam) were determined. A previously developed QSAR model was used to predict the binding affinity of nine designer benzodiazepines that have recently appeared.
Results
Blood-to-plasma values ranged from 0.57 for phenazepam to 1.18 to pyrazolam. Four designer benzodiazepines appearing since 2017 (fluclotizolam, difludiazepam, flualprazolam, and clobromazolam) had predicted binding affinities to the GABA
A
receptor that were greater than previously predicted binding affinities for other designer benzodiazepines.
Conclusions
This work highlights the diverse nature of the designer benzodiazepines and adds to our understanding of their pharmacology. The greater predicted binding affinities are a potential indication of the increasing potency of designer benzodiazepines appearing on the illicit drugs market.
Journal Article
Application of a Bayesian network to aid the interpretation of blood alcohol (ethanol) concentrations in air crashes
•Important to determine if pilots in air crashes were potentially intoxicated.•Bayesian networks allow a rational coherent approach to forensic interpretation.•The model presented allows a more objective approach to case interpretation.•The requirement for further data to strengthen the Network is highlighted.
In the investigation of a fatal air crash, it is important to determine if the pilot, at the time of death, was contravening the regulations in relation to 1) the permitted concentration of ethanol (alcohol) in the blood and 2) whether the pilot had consumed alcohol within a specified period before flying. It is also important to assess whether any alcohol detected in the toxicological samples was present either because of consumption or because of post-mortem alcohol formation. We have developed a Bayesian Network that models the relationships between analytical results, circumstantial evidence and the concentration of alcohol at the time of death in cases of air crash. The model provides a rational, coherent approach to forensic interpretation, moving interpretation from a largely subjective, generalist approach to a more objective, case-specific methodology utilising available relevant data and accommodating the inevitable uncertainties within a case.
Journal Article
The blood-to-plasma ratio and predicted GABA A -binding affinity of designer benzodiazepines
The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the blood-to-plasma ratio. Knowledge of the pharmacodynamics of designer benzodiazepines is also important, and the use of quantitative structure-activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABA
receptor.
In this work, the blood-to-plasma ratios for six designer benzodiazepines (deschloroetizolam, diclazepam, etizolam, meclonazepam, phenazepam, and pyrazolam) were determined. A previously developed QSAR model was used to predict the binding affinity of nine designer benzodiazepines that have recently appeared.
Blood-to-plasma values ranged from 0.57 for phenazepam to 1.18 to pyrazolam. Four designer benzodiazepines appearing since 2017 (fluclotizolam, difludiazepam, flualprazolam, and clobromazolam) had predicted binding affinities to the GABA
receptor that were greater than previously predicted binding affinities for other designer benzodiazepines.
This work highlights the diverse nature of the designer benzodiazepines and adds to our understanding of their pharmacology. The greater predicted binding affinities are a potential indication of the increasing potency of designer benzodiazepines appearing on the illicit drugs market.
Journal Article
Evidence based survey of the distribution volume of ethanol: Comparison of empirically determined values with anthropometric measures
•Blood-alcohol calculations are often required in forensic science casework and commonly involve the Widmark equation.•Anthropometric equations can tailor Widmark’s rho-factor for a given individual.•Results using anthropometric equations were in reasonably good agreement with rho-factors determined empirically.•A regression equation involving the person’s age, height and body weight was the best model for male subjects.•Consideration of the person’s BMI gave more accurate results for females.
The Widmark equation is commonly used when blood alcohol calculations are required in forensic and legal medicine, such as in road-traffic cases and alcohol-related deaths. An important biological variable in this connection is the volume of distribution (Vd) of ethanol, which is commonly referred to as the rho-factor. Although a person’s Vd can be determined empirically through controlled drinking experiments, this approach is not very practical in reality. For this reason, a number of anthropometric equations have been developed that utilize sex, age, height and weight to estimate the person’s total body water (TBW) and hence Vd of ethanol. To date, there are not any studies that compare Vd derived from anthropometric data with robust values measured empirically. From the literature we compiled information about the Vd of ethanol from drinking studies with 173 Caucasian males and 63 Caucasian females from Western Europe. These empirically derived values of Vd were then compared with estimates derived from various anthropometric equations. In males the Watson, Watson and Batt regression equation involving age, height and weight gave the most accurate results (bias was 0.00L/kg) and 95% range ±0.13L/kg. The equation derived by Forrest, which took into consideration a person’s body mass index (BMI), gave the best estimates of Vd for females; mean bias −0.01L/kg and range ±0.15L/kg.
Journal Article
Using μX-Ray CT to observe postmortem diffusion from the stomach in a rat model
•Postmortem diffusion of drugs from stomach can hinder interpretation.•μX-Ray CT can visualise postmortem diffusion from the stomach in a rat model.•Body position influences direction of diffusion from stomach.•Most diffusion from the stomach occurs within the first 24h.
The stomach has long been recognised as a depot for postmortem diffusion. A better understanding of the phenomena of postmortem diffusion would aid forensic practitioners in their interpretation of toxicological results. A limitation of previous stomach diffusion studies was the lack of ability to visualise postmortem diffusion in real time, the use of μX-ray Computed Tomography (CT) could overcome this problem. We utilised CT to track the diffusion of the contrast medium caesium ions (Cs+) (administered by oral gavage) from the rat stomach over 6 days. We investigated the influence of temperature (4°C and 20°C) and body position (horizontal and vertical). The results show that the a) diffusion of Cs+ from the stomach can be visualised over 6 days, over which a significant amount (∼50%) of the diffusion occurs in the first 24h following administration; b) storing the rat at 4°C reduces the distance of diffusion from the stomach by ∼66%; c) body position influences the route of diffusion and d) in 2 of the 16 rats studied Cs+ was found in the right lobe of the liver. Overall these results show that CT using Cs+ is a good model to visualise postmortem diffusion and that bodies show significant variation in postmortem diffusion. It is also clear that bodies should be refrigerated and postmortem samples should be taken as soon as possible to minimise the influences of postmortem diffusion from the stomach.
Journal Article
Total body water is the preferred method to use in forensic blood-alcohol calculations rather than ethanol’s volume of distribution
•Blood-alcohol calculations are often required in forensic science casework.•The Widmark equation is commonly used for this purpose.•Total body water (TBW) gives more accurate results than distribution volume.•An equation involving TBW was applicable to several different ethnic groups.•The TBW equation was valid for people with a widely different body mass index.
During the prosecution and defence of drink-driving cases, forensic practitioners are often required to engage in various blood-alcohol calculations, such as whether or not the statutory limit was exceeded (e.g. 80mg/100mL, 0.08g/100mL or 0.80g/L). For this purpose, most forensic scientists utilize the Widmark equation, or some modification thereof, to calculate a person’s blood alcohol concentration (BAC) based on information about the amount of ethanol consumed and the pattern of drinking. This equation comes in two main forms; one of which incorporates the apparent volume of distribution of ethanol (V) and the other a person’s total body water (TBW). In this study, we utilised two independent data sets, one involving the determination of V for ethanol in 173 men and 63 women, and the other TBW determined for 582 men and 884 women. Those subjects included in the TBW group represented various racial groups (Caucasians, African Americans, Hispanics, Asians and Puerto Ricans), with body mass index (BMI) ranging from 17 to 80kg/m2. Both versions of the Widmark equation were evaluated in relation to their accuracy and precision in predicting TBW and/or V using the two most common anthropometric equations; those of Watson et al. and Forrest. Both anthropometric equations exhibited good accuracy (<4.3%) for the prediction of both TBW and V. However, the root mean square error was lower TBW was used for prediction (9.09–12.84%) rather than V (11.72–15.08%). Overall, this study has demonstrated (a) that blood-alcohol calculations are more reliable using TBW rather than V (b) that both equations (Watson et al. and Forrest) are applicable to ethnic groups other than Caucasians and (c) the Forrest equation predicts TBW in men and women with BMI from 17 to 35kg/m2 and that the Watson et al. equation works for those with more extreme BMI; females (17–80kg/m2) and males (17–67kg/m2).
Journal Article
Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N‐methyl‐D‐aspartate receptors
Human α7 nicotinic acetylcholine (ACh) receptors were expressed in Xenopus oocytes and the effects of the N‐methyl‐D‐aspartate (NMDA) receptor open channel blockers memantine and cerestat on this receptor were examined using two‐electrode voltage‐clamp recordings and 125I‐α‐bungarotoxin (125I‐α‐bgtx) binding. Memantine and cerestat produced complete inhibition of ACh‐induced inward currents with affinities similar to that reported for native NMDA receptors. Cerestat, IC50 1.7 (−1; +2) μM, was more potent than memantine, IC50 5 (−3;+8) μM, and the effects of both drugs were fully and rapidly reversible. Inhibition of α7 receptor function was voltage‐independent, and it occurred at concentrations far lower than those needed to inhibit (never completely) binding of 125I‐α‐bgtx to α7 receptors, suggesting that the effects of memantine or cerestat are noncompetitive. These results provide evidence that human α7 receptors are inhibited by memantine and cerestat and suggest that caution should be applied when using these compounds to study systems in which NMDA and nACh receptors co‐exist. British Journal of Pharmacology (2003) 140, 1313–1319. doi:10.1038/sj.bjp.0705559
Journal Article
Forensic science education and training
A comprehensive and innovative guide to teaching, learning and assessment in forensic science education and practitioner training Includes student exercises for mock crime scene and disaster scenarios Addresses innovative teaching methods including apps and e-gaming Discusses existing and proposed teaching methods.
eBook
Use of the Randox Evidence Investigator immunoassay system for near-body drug screening during post-mortem examination in 261 forensic cases
•The Evidence Investigator screens for a range of drugs in postmortem specimens.•Qualitative results can be obtained in the time it takes to complete an autopsy.•Assay results for each specimen was in good agreement with confirmatory analysis
This paper describes the performance of four Randox drug arrays, designed for whole blood, for the near-body analysis of drugs in a range of post-mortem body specimens.
Liver, psoas muscle, femoral blood, vitreous humor and urine from 261 post-mortem cases were screened in the mortuary and results were obtained within the time taken to complete a post-mortem. Specimens were screened for the presence of amfetamine, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, cannabinoids, dextropropoxyphene, fentanyl, ketamine, lysergide, methadone, metamfetamine, methaqualone, 3,4-methylenedioxymetamfetamine, opioids, paracetamol, phencyclidine, salicylate, salicylic acid, zaleplon, zopiclone and zolpidem using the DOA I, DOA I+, DOA II and Custom arrays.
Liver and muscle specimens were obtained from each of the 261 post-mortem cases; femoral blood, vitreous humor and urine were available in 98%, 92% and 72% of the cases, respectively. As such, the equivalent of 12,978 individual drug-specific, or drug-group, immunoassay tests were undertaken. Overall >98% of the 12,978 screening tests undertaken agreed with laboratory confirmatory tests performed on femoral blood.
There is growing interest in the development of non-invasive procedures for determining the cause of death using MRI and CT scanning however these procedures are, in most cases, unable to determine whether death may have been associated with drug use. The Randox arrays can provide qualitative and semi-quantitative results in a mortuary environment enabling pathologists to decide whether to remove specimens from the body and submit them for laboratory analysis. Analysis can be undertaken on a range of autopsy specimens which is particularly useful when conventional specimens such as blood are unavailable.
Journal Article