| 1. |
- Do, Ron, et al.
(author)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Journal article (peer-reviewed)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 2. |
- Willer, Cristen J., et al.
(author)
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Discovery and refinement of loci associated with lipid levels
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Journal article (peer-reviewed)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 3. |
- Helander, Anders, et al.
(author)
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Bestämning av alkohol i utandningsluft kan ge fel mätvärde : Varning för ospecifik testning med vissa instrument
- 2010
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In: Läkartidningen. - : Lakartidningen. - 0023-7205 .- 1652-7518. ; 107:3, s. 110-112
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Journal article (peer-reviewed)abstract
- Alkoholutandningsprov används vid polisens trafiknykterhetskontroller men även inom sjukvården och kriminalvården samt allt oftare i arbetslivet.Dagens utandningsapparater för etanol baseras på antingen halvledarteknik, bränslecell eller infraröd detektion.Halvledarinstrumenten är billiga men ospecifika för etanol och kan även reagera på andra ämnen som förekommer i utandningsprov.Mätmetoder med dålig analytisk specificitet innebär alltid en risk för falskt positiva resultat.Eftersom ett falskt positivt alkoholutandningsprov kan få mycket allvarliga konsekvenser för den enskilde, bör endast användning av säkra instrument baserade på bränslecell eller infraröd detektion accepteras i legala sammanhang.
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| 4. |
- Jones, Alan Wayne, et al.
(author)
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Amphetamine Abuse in Sweden : Subject Demographics, Changes in Blood Concentrations Over Time, and the Types of Coingested Substances
- 2013
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In: Journal of Clinical Psychopharmacology. - : Lippincott Williams & Wilkins. - 0271-0749 .- 1533-712X. ; 33:2, s. 248-252
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Journal article (peer-reviewed)abstract
- Amphetamine is a major drug of abuse in Sweden and in the other Nordic countries. The demographics of amphetamine abusers in Sweden and the concentrations of this stimulant in blood are reported for 10 years of forensic blood samples (2001-2010). Using a forensic toxicology database (TOXBASE), we studied 1183 amphetamine-related deaths, 20,452 users of illicit drugs, and 47,366 people arrested for driving under the influence of drugs (DUID). Most amphetamine abusers were male (82%-87%), and their average age was 33 to 39 years with males being 2 to 3 years older than females (P andlt; 0.001). Mean (median) concentrations of amphetamine in blood were 1.25 (0.40) mg/L in autopsy cases, 0.61 (0.40) mg/L in users of illicit drugs, and 0.76 (0.58) mg/L in DUID suspects. Median concentration in DUB) suspects was significantly higher than in the other forensic materials (P andlt; 0.001). Women also had higher median concentrations of amphetamine in blood than male abusers of this central stimulant (P andlt; 0.001). The major coingested drugs were benzodiazepines (41%), cannabis (26%), opiates (21%), and alcohol (18%) in autopsy cases. Polydrug use was less common in DUID suspects and users of illicit drugs, although benzodiazepines (13%), tetrahydrocannabinol (12%), and opiates (5%) were often identified along with amphetamine. Because median concentration of amphetamine was higher in living subjects (DUID suspects) compared with amphetamine-related deaths, this points toward toxicity of coingested drugs or adverse drug-drug interaction as being responsible for death.
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| 5. |
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| 6. |
- Jones, Alan Wayne
(author)
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Concentration units used to report blood- and breath-alcohol concentration for legal purposes differ between countries which is important to consider when blood/breath ratios of alcohol are compared and contrasted
- 2024
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In: Journal of Forensic Sciences. - : WILEY. - 0022-1198 .- 1556-4029.
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Journal article (peer-reviewed)abstract
- This technical note reviews the plethora of concentration units used to report blood-alcohol concentration (BAC) and breath-alcohol concentrations (BrAC) for legal purposes in different countries. The choice of units sometimes causes confusion when scientific papers originating from a certain country might be introduced into evidence via expert testimony, such as when alcohol-related crimes are prosecuted. The concentration units are also important to consider when blood/breath ratios (BBRs) of alcohol are calculated and compared between countries. Statutory BAC limits for driving in most nations are reported in mass/volume (m/v) units, such as g/100 mL (g%) in the United States, mg/100 mL (mg%) in the United Kingdom and Republic of Ireland, or g/L (mg/mL) in many EU nations. By contrast, Germany and the Nordic countries report BAC as mass/mass (m/m) units, hence g/kg or mg/g, which are similar to 5.5% lower than m/v units, because whole blood has an average density of 1.055 g/mL. There are historical reasons for reporting BAC in mass/mass units because the aliquots of blood analyzed were measured by weight rather than volume. The difference between m/m and m/v is also important in postmortem toxicology, such as when distribution ratios of ethanol between blood and other biological specimens, such as urine, vitreous humor, and cerebrospinal fluid, are reported.
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| 7. |
- Jones, Alan Wayne
(author)
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Dubowski's stages of alcohol influence and clinical signs and symptoms of drunkenness in relation to a person's blood-alcohol concentration-Historical background
- 2024
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403.
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Research review (peer-reviewed)abstract
- This article traces the origin of various charts and tables delineating the stages of alcohol influence in relation to the clinical signs and symptoms of drunkenness and a person's blood-alcohol concentration (BAC). In forensic science and legal medicine, the most widely used such table was created by Professor Kurt M. Dubowski (University of Oklahoma). The first version of the Dubowski alcohol table was published in 1957, and minor modifications appeared in various articles and book chapters until the final version was published in 2012. Seven stages of alcohol influence were identified including subclinical (sobriety), euphoria, excitement, confusion, stupor, alcoholic coma and death. The BAC causing death was initially reported as 0.45+ g%, although the latest version cited a mean and median BAC of 0.36 g% with a 90% range from 0.21 g% to 0.50 g%. An important feature of the Dubowski alcohol table was the overlapping ranges of BAC for each of the stages of alcohol influence. This was done to reflect variations in the physiological effects of ethanol on the nervous system between different individuals. Information gleaned from the Dubowski table is not intended to apply to any specific individual but more generally for a population of social drinkers, not regular heavy drinkers or alcoholics. Under real-world conditions, much will depend on a person's age, race, gender, pattern of drinking, habituation to alcohol and the development of central nervous tolerance. The impairment effects of ethanol also depend to some extent on whether observations are made on the rising or declining phase of the blood-alcohol curve (Mellanby effect). There will always be some individuals who do not exhibit the expected behavioral impairment effects of ethanol, such as regular heavy drinkers and those suffering from an alcohol use disorder.
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| 8. |
- Jones, Alan Wayne
(author)
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Fatality from Drinking Denatured Alcohol and Hypothermia
- 2011
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In: JOURNAL OF ANALYTICAL TOXICOLOGY. - : Preston Publications Inc. - 0146-4760. ; 35:5, s. 316-318
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Journal article (peer-reviewed)abstract
- A 19-year-old non-diabetic female suffering from irritable bowel syndrome was found unconscious outdoors in the month of October. She was severely hypothermic and rushed to hospital for life-saving treatment. Evidence emerged that the victim had attempted suicide by drinking denatured alcohol (T-Red). According to the manufacturer of this product, it contains > 85% (v/v) ethanol, ∼5% (v/v) acetone, 1-2% (v/v) ethyl acetate, and ∼3% (v/v) methyl ethyl ketone (MEK), but no isopropanol. A venous blood sample taken on admission to hospital contained ethanol (660 mg/100 mL), acetone (25 mg/100 mL), isopropanol (78 mg/100 mL), and MEK, although the latter was not quantified. Despite intensive care, the patient died 21 h after admission and postmortem femoral blood contained ethanol (390 mg/100 mL), acetone (14 mg/100 mL), isopropanol (53 mg/100 mL), and MEK. During oxidative metabolism of ethanol, there is a shift in the redox state of the liver to a more reduced potential as reflected in a raised NADH/NAD+ ratio, which impacts on other NAD-dependent biochemical reactions, including reduction of acetone to isopropanol. The lower concentrations of ethanol, acetone, and isopropnaol in postmortem blood compared with antemortem blood indicate the metabolism of these substances during the 21-h survival period when the patient received emergency hospital treatment.
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| 9. |
- Jones, Alan Wayne, et al.
(author)
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High prevalence of previous arrests for illicit drug use and/or impaired driving among drivers killed in motor vehicle crashes in Sweden with amphetamine in blood at autopsy
- 2015
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In: International journal on drug policy. - : Elsevier. - 0955-3959 .- 1873-4758. ; 26:8, s. 790-793
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Journal article (peer-reviewed)abstract
- Background: Amphetamine, and to a lesser extent the secondary amine methamphetamine, are major recreational drugs of abuse in Sweden. These central stimulant amines are identified in blood from roughly 50% of people arrested for driving under the influence of drugs (DUID). However, much less information is available about the presence of amphetamine in blood of drivers killed in road-traffic crashes.Methods: This retrospective 10-year study (2001-2010) used a forensic toxicology database (TOXBASE) to retrieve information about road-traffic crashes when the driver had amphetamine and/or methamphetamine in autopsy blood. Forensic toxicology results were available from over 95% of all drivers killed on Swedish roads during this 10-year period.Results: Amphetamine was present in the blood of 106 drivers (3.9%) either alone or together with other psychoactive substances (e.g. alcohol, cannabis, diazepam, alprazolam, etc.). The vast majority of fatalities were male (95%) with a mean age (+/- standard deviation) of 37 +/- 11.4 years (range 16-67 years). The mean (median) and highest concentrations of amphetamine in femoral blood were 1.36 mg/L (1.0 mg/L) and 6.74 mg/L, respectively. Many of the victims (75%) had been arrested previously for use of illicit drugs or DUID. The median number of previous arrests was 4 (range 0-83) and amphetamine or methamphetamine were among the drugs identified in blood samples from 89% of cases (0-100%).Conclusion: The high prevalence of repeat DUID offending and/or use of illicit drugs among the drivers killed in road-traffic crashes suggests that an early intervention and treatment for stimulant abuse might have been more beneficial than conventional punishments for such drug-related crimes. (C) 2015 Elsevier B.V. All rights reserved.
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| 10. |
- Jones, Alan Wayne
(author)
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Perspectives in Drug Discovery : Central Nervous System Depressants
- 2014
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In: TIAFT Bulletin. - 1103-7660. ; :44, s. 5-16
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Journal article (other academic/artistic)abstract
- This collection of short essays deal with the history of drug discovery and covers a wide range of pharmaceutical substances, including prescription medication as well as illicit recreational drugs of abuse. Consideration was also given to the plethora of drugs encountered in routine forensic casework, especially in traffic crimes, such as driving under the influence of drugs (DUID) and in post-mortem toxicology when drug poisoning deaths are investigated. The essays were written over a number of years and reflect to a large extent my own interests and reading about the history of pharmacology and toxicology of drugs. Background information about the chemistry and pharmacology of many of the most commonly encountered drugs and poisons is presented and this should prove useful in the training of newly recruited staff as well as students starting their studies in pharmacology and toxicology. One aim of the essays was to highlight the human side of pharmacology in medicine by providing details about the scientists who are credited with making the crucial observation when a new therapeutic agent was discovered. Another aim was to highlight the role of serendipity in drug discovery. Abbreviated versions of the essays are scheduled to appear in consecutive issues of the bulletin of The International Association of Forensic Toxicologists (TIAFT).
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| 11. |
- Jones, Alan Wayne
(author)
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The Variability of the Blood/Breath Ratio and Its Impact on the Results of Breath-Alcohol Analyses: A Rejoinder
- 2024
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In: Journal of Chemical Education. - : AMER CHEMICAL SOC. - 0021-9584 .- 1938-1328. ; 101:3, s. 715-717
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Journal article (other academic/artistic)abstract
- The Journal of Chemical Education (JCE) recently published a letter to the editor by Dominick Labianca that was critical of methods of breath alcohol analysis because of biological variability in the blood/breath ratio (BBR) of alcohol (). His opinions deserve further comment and discussion. As background information, breath-alcohol instruments are used for two main purposes: (i) as a roadside screening test of driver sobriety and (ii) evidential quality instruments are used to generate evidence for prosecution of traffic offenders. Variations in the BBR are irrelevant in jurisdictions that enforce a statutory breath-alcohol concentration (BrAC) limit for driving, such as 0.08 g/210 L in USA. Such legislation makes it unnecessary to convert BrAC into the coexisting blood-alcohol concentration (BAC) for legal purposes. Variability in the BBR is explained by various physiological factors, such as lung function and the volume of breath discarded before a sample is captured for analysis. Moreover, BrAC is more closely related to ethanol concentration in arterial blood rather than cubital venous blood, which is the specimen used for analysis in forensic casework. In those jurisdictions that might convert BrAC into the coexisting BAC, the use of a 2100:1 BBR as a calibration factor underestimates the true venous BAC in the majority of cases.
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| 12. |
- Jones, Alan Wayne, et al.
(author)
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What non-alcohol drugs are used by drinking drivers in Sweden? Toxicological results from ten years of forensic blood samples
- 2012
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In: Journal of Safety Research. - : Elsevier. - 0022-4375 .- 1879-1247. ; 43:3, s. 151-156
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Journal article (peer-reviewed)abstract
- Introduction and Method: Using a forensic toxicology database (TOXBASE), the toxicological results from 10 years of forensic blood samples from people arrested for driving under the influence of alcohol and/or other drugs were reviewed. Results: Alcohol was the only drug identified in blood in N = 35,704 cases at a median blood-alcohol concentration (BAC) of 1.63 mg/g. The mean age (+/- SD) of these offenders was 40 +/- 15 years and 89% were male. The median BAC was lower (1.30 mg/g) in drivers who had consumed alcohol and used a prescription drug before driving (N = 1,251). The mean age of this group of traffic offenders was 38 +/- 13 years and 85% were male. Both the median BAC (0.97 mg/g) and the mean age were lowest (36 +/- 11 years, 92% male) in N = 3,153 drivers who had consumed alcohol and used illicit drugs before driving. Cannabis, amphetamine, cocaine and morphine (metabolite of heroin) were the commonest illicit drugs identified in blood samples. Sedative-hypnotics (benzodiazepines) were the major prescription drugs co-ingested with alcohol. Poly-drug use was a common finding in these traffic delinquents, although individuals who only drank alcohol had a higher median BAC and were also several years older than drinking drivers combining alcohol with other drugs before driving. Impact on Industry: Zero-tolerance legislation did not deter hard-core offenders. In future there should be more focus on treatment for alcohol and substance abuse disorder rather than conventional punishments for this type of traffic crime.
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| 13. |
- Kugelberg, Fredrik, et al.
(author)
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Forensic toxicology findings in deaths involving gamma-hydroxybutyrate
- 2010
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In: International journal of legal medicine. - : Elsevier. - 0937-9827 .- 1437-1596. ; 124:1
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Journal article (peer-reviewed)abstract
- Concentrations of the illicit drug gamma-hydroxybutyrate (GHB) were determined in femoral venous blood and urine obtained at autopsy in a series of GHB-related deaths (N = 49). The analysis of GHB was done by gas chromatography after conversion to gamma-butyrolactone and quantitation of the latter with a flame ionization detector. The cutoff concentration of GHB in femoral blood or urine for reporting positive results was 30 mg/L. The deceased were mainly young men (86%) aged 26.5 +/- 7.2 years (mean +/- SD), and the women (14%) were about 5 years younger at 21.4 +/- 5.0 years. The mean, median, and highest concentrations of GHB in femoral blood (N = 37) were 294, 190, and 2,200 mg/L, respectively. The mean urine-to-blood ratio of GHB was 8.8, and the median was 5.2 (N = 28). In 12 cases, the concentrations of GHB in blood were negative (less than 30 mg/L) when the urine contained 350 mg/L on average (range 31-1,100 mg/L). Considerable poly-drug use was evident in these GHB-related deaths: ethanol (18 cases), amphetamine (12 cases), and various prescription medications (benzodizepines, opiates, and antidepressants) in other cases. Interpreting the concentrations of GHB in postmortem blood is complicated because of concomitant use of other psychoactive substances, variable degree of tolerance to centrally acting drugs, and the lack of reliable information about survival time after use of the drug.
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| 14. |
- Lindblad-Toh, Kerstin, et al.
(author)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Journal article (peer-reviewed)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 15. |
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| 16. |
- Olds, Maria L., et al.
(author)
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Preanalytical factors influencing the results of ethanol analysis in postmortem specimens
- 2024
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In: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 48:1, s. 9-26
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Research review (peer-reviewed)abstract
- Excessive drinking and drunkenness are underlying factors in many fatal accidents, which make the quantitative determination of ethanol in postmortem (PM) specimens an essential part of all unnatural death investigations. The same analytical methods are used to determine ethanol in blood taken from living and deceased persons although the interpretation of the results is more complicated in medical examiner cases owing to various preanalytical factors. The biggest problem is that under anaerobic conditions ethanol can be produced naturally in decomposed bodies by microbial activity and fermentation of blood glucose. Ways are needed to differentiate antemortem ingestion of ethanol from PM synthesis. One approach involves the determination of ethanol in alternative specimens, such as bile, cerebrospinal fluid, vitreous humor and/or urine, and comparison of results with blood alcohol concentration (BAC). Another approach involves the analysis of various alcohol biomarkers, such as ethyl glucuronide, ethyl sulfate and/or phosphatidylethanol or the urinary metabolites of serotonin 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5-HIAA/5-HTOL). If ethanol had been produced in the body by microbial activity, the blood samples should also contain other low-molecular volatiles, such as acetaldehyde, n-propanol and/or n-butanol. The inclusion of 1-2% w/v sodium or potassium fluoride, as an enzyme inhibitor, in all PM specimens is essential to diminish the risk of ethanol being generated after sampling, such as during shipment and storage prior to analysis. Furthermore, much might be gained if the analytical cut-off for reporting positive BAC was raised from 0.01 to 0.02 g% when PM blood is analyzed. During putrefaction low BACs are more often produced after death than high BACs. Therefore, when the cadaver is obviously decomposed, a pragmatic approach would be to subtract 0.05 g% from the mean analytical result. Any remaining BAC is expected to give a more reliable indication of whether alcohol had been consumed before death.
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