Authenticating the Vocabulary: A Study in Seventeenth-Century Lexicographical Practice

Thomas Blount is unique among English compilers of the seventeenth century in systematically naming books and authors as evidence for the use of words entered in his dictionary. Such documentation of the vocabulary would now be associated with scholarly historical dictionaries such as the Johnson and the OED, rather than with a small dictionary for general use. In his Glossographia (1656) Blount differs from these by referring mainly to contemporary writings (and without giving quotations) and in being selective in his attestations, for about one in twenty of all entries. An analysis is presented of the types of words thus treated, and of the varied purposes served by his references to external sources: he sees the need to authenticate the less stable parts of the English vocabulary of his day - neologisms, exotic terms, semi-technical and learned words. Blount probably derived this lexicographical technique from the Latin dictionaries of his time. A century earlier than Dr Johnson, he confronted some of the same problems in justifying entries made in his dictionary, and produced different but equaIly valid answers to them

The evaluation of dual laser handheld raman spectroscopy for identifying novel psychoactive substances

Novel psychoactive substances have been increasing over the last decade with more than 450 derivatives available on the market. The issue with novel psychoactive substances is much more complicated than their effects/side effects. Hence, these substances often contain mixtures of pharmacologically active/inactive impurities which interfere with their effects. The accelerated development of these substances (at a rate above once a week) urges the need to develop rapid and mobile techniques for their characterisation. Handheld Raman spectroscopy offers the advantage of being quick, nondestructive and specific to chemical entities within the measured analyte. One issue with the Raman signatures of analytes is associated with several variables including the laser wavelength that could be shorter (such as 532 785 nm) or longer wavelength lasers (such as 833 - 1064 nm). Using a longer wavelength laser decreases the fluorescence of the sample, but decreases peak resolution and thus limits the sensitivity of detection. Uptoour knowledge the use of dual laser wavelength for identifying novel psychoactive substances has not been explored. Therefore, this work aims to evaluate the use of dual laser handheld Raman spectroscopy for identifying novel psychoactive substances

Variations in Infant CYP2B6 Genotype Associated with the Need for Pharmacological Treatment for Neonatal Abstinence Syndrome in Infants of Methadone-Maintained Opioid-Dependent Mothers.

Background Neonatal abstinence syndrome (NAS) in infants of methadone-maintained opioid-dependent (MMOD) mothers cannot be predicted in individual cases. We investigated whether variation in infant genotype is associated with severity of NAS. Methods This is a pilot observational cohort study of 21 MMOD mothers and their newborns. Infant buccal swabs were obtained soon after delivery, together with a maternal blood sample for the determination of maternal plasma methadone concentration. Genomic variation in five opioid-related genes (ABCB1, COMT, CYP2B6, CYP2D6, and OPRM1) was ascertained from infant buccal swabs and related to need for pharmacological treatment of NAS. Results Out of 21 infants, 11 (52%) required treatment for NAS. Mothers of treated infants tended to have been prescribed higher doses of methadone, but plasma methadone concentrations did not differ between mothers of treated or untreated babies. Treated and untreated babies did not differ in terms of method of feeding. Treated infants were more likely to carry the normal (homozygous) allele at 516 and 785 regions of CYP2B6 gene (p = 0.015 and 0.023, respectively). There were no differences in any other genes between infants who did or did not require treatment for NAS. Conclusion Genomic variation in CYP2B6 may explain, at least in part, severity of NAS

The effects and toxicity of cathinones from the users' perspectives: A qualitative study.

OBJECTIVE: The objective of this study is to explore the users' perspectives regarding the effects and toxicity of cathinones. METHODS: A systematic search of Internet discussion forums yielded 303 threads relevant to the research objectives. The threads were analysed by conventional content analysis where concepts were developed from codes and themes. RESULTS: The study identified 3 main themes in relation to cathinone use, effects, and toxicity. The first theme considered the modalities of intake of cathinones in relation to the derivative taken (mainly mephedrone, 3-methylmethcathinone, and methylenedioxypyrovalerone), route of administration (eyeballing, insufflation, smoking, intravenous, oral, rectal, and sublingual), multidrug use, and purity of the cathinone derivative. The second theme characterised the main effects of cathinones, that is, increased energy, euphoria, and empathogenic. Toxic effects were reported regarding the nervous system (anxiety, hallucinations, nervousness, and paranoia), cardiovascular system (angina, myocardial infarction, and tachycardia), skin (discolouration, itching, and allergy), and renal system (difficulty in urination). Drug-drug interactions were also reported including multiple drug use between cathinones, stimulants, depressants, and hallucinogens. CONCLUSIONS: The Internet discussion forums provide useful sources of information regarding the effects and toxicity of cathinones, which can be taken into account when assessing the safety of drugs

Hemovigilance: is it making a difference to safety in the transfusion chain?

Hemovigilance is the systematic monitoring of adverse reactions and incidents in the transfusion chain in order to make recommendations for safety improvement. EU member states must have a reporting system for serious adverse reactions or events which might have an effect on quality or safety of blood components. The thesis presents an analysis of routinely collected data on occurrence of blood donation complications and risk factors. A study of procedural and follow-up data from a cohort of related peripheral blood stem cell donors gave no indication of unacceptable risks. In transfused patients an exploratory case-control study found previously undescribed associations with patient characteristics. Using national hemovigilance data the reduction of the risk of TRALI following implementation of male-only plasma was estimated as 33%. Hospitals with a relatively high rate of reported nonserious transfusion reactions were also more likely to have reported one or more transfusion errors, thus this does not support the notion that they might be safer. Hemovigilance reporting has provided insight in short-term risks in the transfusion chain. Additonal methods should be sought for monitoring long-term risks and for promoting measures to bring about safety improvement.Sanquin Blood Supply study grant PPOC 08-008 for study on G-CSF mobilised donors. Printing of this thesis was financially supported by Stichting TRIP (Transfusie- en transplantatiereacties in patiënten) Sanquin Blood Supply Haga Teaching HospitalUBL - phd migration 201

Use of the Randox Evidence Investigator immunoassay system for near-body drug screening during post-mortem examination in 261 forensic cases

BackgroundThis 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.MethodsLiver, 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.ResultsLiver 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.ConclusionsThere 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

Summary statistics for drug concentrations in post-mortem femoral blood representing all causes of death

Concentration distributions for 183 drugs and metabolites frequently found in post-mortem (PM) femoral venous blood were statistically characterized based on an extensive database of 122 234 autopsy cases investigated during an 18-year period in a centralized laboratory. The cases represented all causes of death, with fatal drug poisonings accounting for 8%. The proportion of males was 74% with a median age of 58 years compared with 26% females with a median age of 64 years. In 36% of these cases, blood alcohol concentration was higher than or equal to 0.2 parts per thousand, the median being 1.6 parts per thousand. The mean, median, and upper percentile (90th, 95th, 97.5th) drug concentrations were established, as the median PM concentrations give an idea of the "normal" PM concentration level, and the upper percentile concentrations indicate possible overdose levels. A correspondence was found between subsets of the present and the previously published PM drug concentrations from another laboratory that grouped cases according to the cause of death. Our results add to the knowledge for evidence-based interpretation of drug-related deaths.Peer reviewe

On-spot quantification of modafinil in generic medicines purchased from the Internet using handheld Fourier transform-infrared, near-infrared and Raman spectroscopy

Poor quality medicines represent an expanding global public health threat facilitated by the Internet. A recent survey showed that one in five students have used modafinil to enhance learning ability mainly purchased from Internet sources. The aim of this work was to develop on-the-spot and simple methods for the quantification of modafinil in generic medicines using Fourier transform-infrared (FTIR), near-infrared (NIR) and Raman spectroscopy along with partial least square regression (PLSR). Modafinil tablets were measured in intact form using NIR and Raman and in powdered form using FTIR, NIR and Raman. Additionally, powder mixtures of crushed modafinil tablets and excipient(s) were prepared either by diluting the crushed tablets with excipient(s), or sequentially adding excipient(s) to the crushed tablets. Three PLSR models were constructed in MATLAB 2014a from powder mixtures and two from intact and powdered tablets. For FTIR and Raman spectroscopy, PLSR models based on tablets gave linear calibration curve with correlation coefficient (r2) values above 0.94 and a root mean square error of calibration (RMSEC) below 0.96% m/m. Conversely, the PLSR model based on powder sequential addition gave the highest accuracy using the NIR spectra (r2 = 0.99, RMSEC = 1.15% m/m). The latter model showed accuracy in predicting the concentration of the active pharmaceutical ingredient in modafinil generic medicines proving their authenticity. The overall results showed that the combination of the three spectroscopic methods with PLSR offered a rapid technique for authenticating generic modafinil medicines

Drug concentrations in post-mortem femoral blood compared with therapeutic concentrations in plasma

Peer reviewe