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  • 1.
    Aarts, B.
    et al.
    Netherlands Forensic Institute, Biological Traces and DNA, The Hague, Netherlands.
    Kokshoorn, B.
    Netherlands Forensic Institute, Biological Traces and DNA, The Hague, Netherlands.
    Mc Kenna, L.G.
    Forensic Science Ireland, DNA department, Dublin, Ireland.
    Drotz, W.
    Swedish National Forensic Centre, DNA department, Linköping, Sweden.
    Ansell, Ricky
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish National Forensic Centre, DNA department, Linköping, Sweden.
    van Oorschot, R.A.
    Office of the Chief Forensic Scientist, Victoria Police Forensic Services Department, Macleod- Victoria, Australia.
    Kloosterman, A.D.
    Netherlands Forensic Institute, Biological Traces and DNA, The Hague, Netherlands.
    DNActivity: International cooperation in activity level interpretation of forensic DNA evidence.2015In: Abstract book, 7th European Academy of Forensic Science, EAFS, Prag, Tjeckien, 2015., 2015, p. 555-Conference paper (Other academic)
    Abstract [en]

    Questions posed to expert witnesses by the legal community and the courts are expanding to include not just those relating to source level (i.e. ‘who is the donor of the trace?’) but also those relating to activitity level (i.e. ‘how did the DNA get there?’). The answers to these questions are usually formulated as the probability of the evidence under alternative scenarios. As activity level questions are part of investigative and legal considerations it is of paramount importance that expert witnesses are provided with knowledge and tools to address these questions.

    To answer such questions within a probabilistic framework, empirical data is needed to estimate probabilities of transfer, persistence and recovery of DNA as well as background levels of DNA on everyday objects. There is a paucity of empirical data on these topics, but the number of studies is increasing both through in-house experiments and experimental data published in international scientific journals.

    Laboratories that conduct such studies all use different experimental setups, trace recovery strategies and techniques and DNA analysis systems and equipment. It is essential for the forensic genetics community in general to establish whether the data generated by different labs are in concordance, and can therefore be readily used by the forensic community.

    Moreover, if existing data and data generated from future experiments are made available to the (forensic) community, knowledge is needed on the key factors that underlie potential interlaboratory variation.

    The aims and objectives of this ENFSI Monopoly 2013 project are to conduct a study of methodologies and data from different laboratories and to assess the comparability of the scientific data on transfer, persistence and recovery of DNA. This comparison will allow us to identify key factors that underlie potential variation. This information will be used to setup guidelines to enable sharing and database-storage of relevant scientific

    data. This will improve the ability of forensic scientists and other professionals of the Criminal Justice System to give evidence-based answers to questions that relate to the activity level of the crime under investigation.

  • 2.
    Adolfsson, Emma
    et al.
    Orebro Univ, Sweden.
    Kling, Daniel
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Gunnarsson, Cecilia
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics. Region Östergötland, Regionledningskontoret, Övr Regionledningskontoret.
    Jonasson, Jon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Green, Anna
    Orebro Univ, Sweden.
    Whole exome sequencing of FFPE samples - expanding the horizon of forensic molecular autopsies2023In: International journal of legal medicine, ISSN 0937-9827, E-ISSN 1437-1596, Vol. 137, p. 1215-1234Article in journal (Refereed)
    Abstract [en]

    Forensic molecular autopsies have emerged as a tool for medical examiners to establish the cause of death. It is particularly useful in sudden unexplained deaths where the cause of death cannot be determined with a regular medical autopsy. We provide the first study of exome data from formalin-fixed paraffin-embedded samples (FFPE) paired with data from high-quality blood samples in forensic applications. The approach allows exploration of the potential to use FFPE samples for molecular autopsies and identify variants in extensive exome data. We leverage the high uniformity of the hybridization capture approach provided by Twist Bioscience to target the complete exome and sequence the libraries on a NextSeq 550. Our findings suggest that exome sequencing is feasible for 24 out of a total of 35 included FFPE samples. When successful, the coverage across the exome is comparatively high (> 90% covered to 20X) and uniform (fold80 below 1.5). Detailed variant comparisons for matched FFPE and blood samples show high concordance with few false variants (positive predictive value of 0.98 and a sensitivity of 0.97) with no distinct FFPE artefacts. Ultimately, we apply carefully constructed forensic gene panels in a stepwise manner to find genetic variants associated with the clinical phenotype and with relevance to the sudden unexplained death.

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  • 3.
    Ahlner, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Swedish National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Holmgren, Anita
    Swedish National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Jones, A Wayne
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Swedish National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Demographics and post-mortem toxicology findings in deaths among people arrested multiple times for use of illicit drugs and/or impaired driving2016In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 265, p. 138-143Article in journal (Refereed)
    Abstract [en]

    Background: Multiple arrests for use of illicit drugs and/or impaired driving strongly suggests the existence of a personality disorder and/or a substance abuse problem. Methods: This retrospective study (1993-2010) used a national forensic toxicology database (TOXBASE), and we identified 3943 individuals with two or more arrests for use of illicit drugs and/or impaired driving. These individuals had subsequently died from a fatal drug poisoning or some other cause of death, such as trauma. Results: Of the 3943 repeat offenders 1807 (46%) died from a fatal drug overdose and 2136 (54%) died from other causes (p amp;lt; 0.001). The repeat offenders were predominantly male (90% vs 10%) and mean age of drug poisoning deaths was 5 y younger (mean 35 y) than other causes of death (mean 40 y). Significantly more repeat offenders (46%) died from drug overdose compared with all other forensic autopsies (14%) (p amp;lt; 0.001). Four or more drugs were identified in femoral blood in 44% of deaths from poisoning (drug overdose) compared with 18% of deaths by other causes (p amp;lt; 0.001). The manner of death was considered accidental in 54% of deaths among repeat offenders compared with 28% for other suspicious deaths (p amp;lt; 0.001). The psychoactive substances most commonly identified in autopsy blood from repeat offenders were ethanol, morphine (from heroin), diazepam, amphetamines, cannabis, and various opioids. Conclusions: This study shows that people arrested multiple times for use of illicit drugs and/or impaired driving are more likely to die by accidentally overdosing with drugs. Lives might be saved if repeat offenders were sentenced to treatment and rehabilitation for their drug abuse problem instead of conventional penalties for drug-related crimes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 4.
    Ahlström, Stina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Sweden.
    Thiblin, Ingemar
    Natl Board Forens Med, Sweden; Uppsala Univ, Sweden.
    Jönsson, Anna K
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Characteristics of post-mortem beta-hydroxybutyrate-positivet cases - A retrospective study on age, sex and BMI in 1407 forensic autopsies2021In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 325, article id 110878Article in journal (Refereed)
    Abstract [en]

    Background: Post-mortem biochemistry, including the analysis of beta-hydroxybutyrate (BHB), is increasingly employed in forensic medicine, especially in conditions such as diabetes and chronic alcoholism. However, not much is known about the associations between age, body mass index (BMI), and sex and BHB concentrations in ketoacidotic conditions. Aim: To retrospectively study the association between age, BMI and sex in several conditions, such as diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA), and elevated post-mortem BHB concentrations. Methods: 1407 forensic autopsy cases analysed for BHB were grouped by diagnosis: DKA, AKA, HHS [hyperosmolar hyperglycaemic state], acidosis NOS [not otherwise specified], or hypothermia. Age, sex, BMI and the concentrations of blood alcohol, vitreous glucose and blood BHB were recorded. Results: Cases of AKA and DKA were most numerous (184 and 156, respectively). In DKA and in its male subgroup, cases with severe ketosis (BHB > 1000 mu g/g) were younger and had a lower BMI than those with moderate ketosis (BHB 250-1000 mu g/g) and controls (P < 0.001). In DKA and in its female subgroup, cases with moderate ketosis cases were older (P = 0.0218 and P = 0.0083) than controls. In AKA and in its male subgroup, cases with severe ketosis had a lower BMI than those with moderate ketosis (P = 0.0391 and P = 0.0469) and controls (P < 0.001). Cases with moderate ketosis had a lower BMI than controls (P < 0.001). Conclusions: BHB concentration is associated with BMI in DKA and AKA, and with both BMI and age in DKA. Constitutional factors should, therefore, be considered in potential AKA and DKA cases. (c) 2021 The Authors. Published by Elsevier B.V. CC_BY_4.0

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  • 5.
    Albinsson, L.
    et al.
    Swedish National Forensic Centre - NFC, Linköping, Sweden.
    Hedman, J.
    Swedish National Forensic Centre - NFC, Linköping, Sweden.
    Ansell, Ricky
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish National Forensic Centre - NFC, Linköping, Sweden.
    Mixed DNA profiles from single-donors2015In: Abstract book, 7th European Academy of Forensic Science, EAFS, Prag, Tjeckien, 2015, 2015, p. 538-Conference paper (Other academic)
    Abstract [en]

    Mosaicism and chimerism in individuals can complicate the interpretation and even lead to misinterpretation of DNA profiles in forensic casework. If a person has different DNA profiles in different tissue types, i.e. a true chimaera, wrongful exclusions can be made. Additionally, mixed chimaeras can have DNA profiles that may be mistaken for mixtures. We have set-up automatic DNA databasing processes to handle atypical single-donor DNA profiles, i.e. profiles having one or several “extra” alleles.

    Studying all reference samples analysed at NFC from 2006 until spring 2014, 2‰ of the samples showed atypical DNA profiles. To be able to set routines for handling these DNA profiles, each one was manually searched in CODIS with adjusted settings, to evaluate the frequency of false-positive hits. To tag these profiles in LIMS a new result status was implemented. Additionally, all such DNA profiles must be confirmed by analysing at least two discrete samples. In LIMS, the results are manually recorded to compose of all alleles from the samples from a suspect, i.e. containing most possible genetic information. LIMS automatically categorises the atypical DNA profiles with a special CODIS index, called “Multi-allelic offender”. The first time an atypical profile is searched, the matches are manually investigated. If a match is false, its disposition will be set to “no match” to prevent this from occurring in future searches. Automatic searches will then be performed in every day routine with moderate stringency, allowing the atypical DNA profile to match either a genotype or a mixture. If the match is true, a match-report will be created and sent to the police from the LIMS.

     

  • 6.
    Ansell, Ricky
    et al.
    National Laboratory of Forensic Science (SKL), Linköping, Sweden.
    Rasmusson, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    A Swedish PerspectiveThe Forensic Use of Bioinformation: Ethical Issues: Nuffield Council on Bioethics2008In: BioSocieties, ISSN 1745-8552, E-ISSN 1745-8560, Vol. 3, no 1, p. 88-92Article in journal (Other academic)
    Abstract [en]

    The Nuffield Report is well-written, clear, extensive and up to date, and it covers most of the major ethical issues in the field of forensic DNA analysis and database searching. The ethical analysis is thorough and based on solid theoretical ground.

  • 7.
    Ansell, Ricky
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish National Forensic Centre, Linköping, Sweden.
    Widén, Christina
    Biology Unit, Swedish National Forensic Centre (NFC), Link€oping, Sweden.
    Swedish Legislation Regarding Forensic DNA Elimination Databases2016In: Forensic Science Policy & Management: An International Journal , ISSN 1940-9044, Vol. 7, no 1-2, p. 20-36Article in journal (Refereed)
    Abstract [en]

    Evidence contaminated with DNA from staff, police, and other individuals can have a dramaticimpact on an investigation and can mislead police inquiries. Forensic DNA elimination databases(EDB) are used to minimize the risks associated with DNA contamination. Central issues withmaintaining such databases include the basis for sample collection, sample, and profile integrity, aswell as retention times, database access, and procedures when a database match occurs. Followingyears of discussion, debate, and the use of an “in house” EDB at the Swedish National ForensicCentre (NFC), these issues have now been resolved by passing legislation on DNA EDB. According tothe legislation, sampling for EDB purposes is mandatory for certain forensic professionals, as well asfor other individuals who need access to the premises handling DNA evidence. In the event of adatabase match, the match can only be reviewed and evaluated for quality purposes and the nameof the donor cannot be disclosed to the crime inquiry. Thus, as a consequence, if a contaminationevent is not the probable cause the legal limitation opens for impunity for individuals included inthe database.KEYWORDSContamination; DNA;elimination database;forensic science; legislationIntroduction

  • 8.
    Arnes, Marit
    et al.
    Oslo Univ Hosp, Norway.
    Bachs, Liliana
    Oslo Univ Hosp, Norway.
    Al Sammarai, Mohammad
    Oslo Univ Hosp, Norway.
    Jones, A Wayne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Hoiseth, Gudrun
    Oslo Univ Hosp, Norway.
    Rate of elimination of gamma-hydroxybutyrate from blood determined by analysis of two consecutive samples from apprehended drivers in Norway2020In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 314, article id 110374Article in journal (Refereed)
    Abstract [en]

    Aim: Gamma-hydroxybutyrate (GHB) is a common drug of abuse with an elimination half-life of 20-45 min. However, there is some evidence that GHB might exhibit saturation kinetics after ingesting high recreational doses. The aim of this study was to investigate the elimination kinetics of GHB from blood in people apprehended by the police for impaired driving and secondary to describe concentrations in all GHB-positive drivers. Methods: Two consecutive blood samples were taken about 30-40 min apart from N =16 apprehended drivers in Norway. GHB was determined in blood by an Ultra High-Performance Liquid ChromatographyTandem Mass Spectrometry (UHPLC-MS/MS) method. The changes in GHB between the two consecutive blood samples allowed estimating GHBs elimination half-life, assuming first-order and zero-order elimination kinetics. GHB concentrations are also reported for N =1276 apprehended drivers with GHB in blood. Results: The median time interval between collecting the two blood samples was 36 min (range 20 56 min). The median concentration of GHB in the first blood sample was 56.5 mg/L (range 14.1 142 mg/L) compared with 47.8 mg/L in the second sample (range 9.75 113 mg/L). The median elimination half-life was 103 min (range 21 187 min), and GHBs median zero-order elimination rate constant was 21.0 mg/L/h (range 6.71-45A mg/L/h). Back-calculation to the time of driving resulted in GHB concentrations up to 820 mg/L assuming first-order kinetics and up to 242 ma assuming zeroorder kinetics. In all drivers (N 1276), the median GHB concentration was 73.7 ma and highest was 484 mg/L. Conclusion: The elimination half-life of GHB in blood samples from apprehended drivers was longer than expected compared with results of controlled dosing studies. Zero-order kinetics seems a more appropriate model for GHB when concentrations are back-calculated. and the median elimination rate was 21 mg/L/h. (C) 2020 The Authors. Published by Elsevier B.V.

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  • 9.
    Ballantyne, Kaye N.
    et al.
    Erasmus MC University, Netherlands Victoria Police Forens Serv Department, Australia .
    Ralf, Arwin
    Erasmus MC University, Netherlands .
    Aboukhalid, Rachid
    Mohammed V Agdal University, Morocco .
    Achakzai, Niaz M.
    University of Punjab, Pakistan .
    Anjos, Maria J.
    National Institute Legal Medical and Forens Science IP, Portugal .
    Ayub, Qasim
    Wellcome Trust Sanger Institute, England .
    Balazic, Joze
    University of Ljubljana, Slovenia .
    Ballantyne, Jack
    University of Central Florida, FL 32816 USA University of Central Florida, FL 32816 USA .
    J. Ballard, David
    Kings Coll London, England .
    Berger, Burkhard
    Medical University of Innsbruck, Austria .
    Bobillo, Cecilia
    University of Buenos Aires, Argentina Consejo Nacl Invest Cient and Tecn, Argentina .
    Bouabdellah, Mehdi
    Mohammed V Agdal University, Morocco .
    Burri, Helen
    University of Zurich, Switzerland .
    Capal, Tomas
    Institute Criminalist Prague, Czech Republic .
    Caratti, Stefano
    University of Turin, Italy .
    Cardenas, Jorge
    University of Santiago de Compostela, Spain .
    Cartault, Francois
    Site Centre Hospital Felix Guyon, Reunion .
    F. Carvalho, Elizeu
    University of Estado Rio De Janeiro, Brazil .
    Carvalho, Monica
    National Institute Legal Medical and Forens Science IP, Portugal .
    Cheng, Baowen
    Yunnan Prov Department Public Secur, Peoples R China .
    D. Coble, Michael
    NIST, MD 20899 USA .
    Comas, David
    University of Pompeu Fabra, Spain .
    Corach, Daniel
    University of Buenos Aires, Argentina Consejo Nacl Invest Cient and Tecn, Argentina .
    E. DAmato, Maria
    University of Western Cape, South Africa .
    Davison, Sean
    University of Western Cape, South Africa .
    de Knijff, Peter
    Leiden University, Netherlands .
    Corazon A. De Ungria, Maria
    University of Philippines, Philippines .
    Decorte, Ronny
    Katholieke University of Leuven, Belgium .
    Dobosz, Tadeusz
    Wroclaw Medical University, Poland .
    M. Dupuy, Berit
    Norwegian Institute Public Heatlh, Norway .
    Elmrghni, Samir
    University of Benghazi, Libya .
    Gliwinski, Mateusz
    Medical University of Gdansk, Poland .
    C. Gomes, Sara
    University of Madeira, Portugal .
    Grol, Laurens
    Netherlands Forens Institute, Netherlands .
    Haas, Cordula
    University of Zurich, Switzerland .
    Hanson, Erin
    University of Central Florida, FL 32816 USA .
    Henke, Juergen
    Institute Blutgruppenforsch LGC GmbH, Germany .
    Henke, Lotte
    Institute Blutgruppenforsch LGC GmbH, Germany .
    Herrera-Rodriguez, Fabiola
    Poder Judicial, Costa Rica .
    R. Hill, Carolyn
    NIST, MD 20899 USA .
    Holmlund, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Honda, Katsuya
    University of Tsukuba, Japan .
    Immel, Uta-Dorothee
    University of Halle Wittenberg, Germany .
    Inokuchi, Shota
    National Research Institute Police Science, Japan .
    A. Jobling, Mark
    University of Leicester, England .
    Kaddura, Mahmoud
    University of Benghazi, Libya .
    S. Kim, Jong
    Supreme Prosecutors Off, South Korea .
    H. Kim, Soon
    National Forens Serv, South Korea .
    Kim, Wook
    Dankook University, South Korea .
    E. King, Turi
    University of Leicester, England .
    Klausriegler, Eva
    Salzburg University, Austria .
    Kling, Daniel
    Norwegian Institute Public Heatlh, Norway .
    Kovacevic, Lejla
    Institute Genet Engn and Biotechnol, Bosnia and Herceg .
    Kovatsi, Leda
    Aristotle University of Thessaloniki, Greece .
    Krajewski, Pawel
    Medical University of Warsaw, Poland .
    Kravchenko, Sergey
    NASU, Ukraine .
    H. D. Larmuseau, Maarten
    Katholieke University of Leuven, Belgium .
    Young Lee, Eun
    Yonsei University, South Korea .
    Lessig, Ruediger
    University of Halle Wittenberg, Germany .
    A. Livshits, Ludmila
    NASU, Ukraine .
    Marjanovic, Damir
    Institute Genet Engn and Biotechnol, Bosnia and Herceg .
    Minarik, Marek
    Genomac Forens Institute, Czech Republic .
    Mizuno, Natsuko
    National Research Institute Police Science, Japan .
    Moreira, Helena
    University of Aveiro, Portugal .
    Morling, Niels
    University of Copenhagen, Denmark .
    Mukherjee, Meeta
    Govt India, India .
    Munier, Patrick
    Site Centre Hospital Felix Guyon, Reunion .
    Nagaraju, Javaregowda
    Centre DNA Fingerprinting and Diagnost, India .
    Neuhuber, Franz
    Salzburg University, Austria .
    Nie, Shengjie
    Kunming Medical University, Peoples R China .
    Nilasitsataporn, Premlaphat
    Royal Thai Police, Thailand .
    Nishi, Takeki
    University of Tsukuba, Japan .
    H. Oh, Hye
    Supreme Prosecutors Off, South Korea .
    Olofsson, Jill
    University of Copenhagen, Denmark .
    Onofri, Valerio
    University of Politecn Marche, Italy .
    U. Palo, Jukka
    University of Helsinki, Finland .
    Pamjav, Horolma
    Minist Public Adm and Justice, Hungary .
    Parson, Walther
    Medical University of Innsbruck, Austria Penn State University, PA 16802 USA .
    Petlach, Michal
    Genomac Forens Institute, Czech Republic .
    Phillips, Christopher
    University of Santiago de Compostela, Spain .
    Ploski, Rafal
    Medical University of Warsaw, Poland .
    P. R. Prasad, Samayamantri
    Centre DNA Fingerprinting and Diagnost, India .
    Primorac, Dragan
    Penn State University, PA 16802 USA University of New Haven, CT USA University of Split, Croatia University of Osijek, Croatia .
    A. Purnomo, Gludhug
    Eijkman Institute Molecular Biol, Indonesia .
    Purps, Josephine
    Charite, Germany .
    Rangel-Villalobos, Hector
    University of Guadalajara CUCienega UdeG, Mexico .
    Rebala, Krzysztof
    Medical University of Gdansk, Poland .
    Rerkamnuaychoke, Budsaba
    Mahidol University, Thailand .
    Rey Gonzalez, Danel
    University of Santiago de Compostela, Spain .
    Robino, Carlo
    University of Turin, Italy .
    Roewer, Lutz
    Charite, Germany .
    Rosa, Alexandra
    University of Madeira, Portugal University of Madeira, Portugal .
    Sajantila, Antti
    University of Helsinki, Finland University of N Texas, TX USA .
    Sala, Andrea
    University of Buenos Aires, Argentina Consejo Nacl Invest Cient and Tecn, Argentina .
    M. Salvador, Jazelyn
    University of Philippines, Philippines .
    Sanz, Paula
    University of Pompeu Fabra, Spain .
    Schmitt, Cornelia
    University of Cologne, Germany .
    K. Sharma, Anil
    Govt India, India .
    A. Silva, Dayse
    University of Estado Rio De Janeiro, Brazil .
    Shin, Kyoung-Jin
    Yonsei University, South Korea .
    Sijen, Titia
    Netherlands Forens Institute, Netherlands .
    Sirker, Miriam
    University of Cologne, Germany .
    Sivakova, Daniela
    Comenius University, Slovakia .
    Skaro, Vedrana
    Genos Ltd, Croatia .
    Solano-Matamoros, Carlos
    University of Costa Rica, Costa Rica .
    Souto, Luis
    University of Aveiro, Portugal .
    Stenzl, Vlastimil
    Institute Criminalist Prague, Czech Republic .
    Sudoyo, Herawati
    Eijkman Institute Molecular Biol, Indonesia .
    Syndercombe-Court, Denise
    Kings Coll London, England .
    Tagliabracci, Adriano
    University of Politecn Marche, Italy .
    Taylor, Duncan
    Forens Science South Australia, Australia Flinders University of S Australia, Australia .
    Tillmar, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden .
    S. Tsybovsky, Iosif
    State Comm Forens Expertises, Byelarus .
    Tyler-Smith, Chris
    Wellcome Trust Sanger Institute, England .
    J. van der Gaag, Kristiaan
    Leiden University, Netherlands .
    Vanek, Daniel
    Forens DNA Serv, Czech Republic Charles University of Prague, Czech Republic .
    Volgyi, Antonia
    Minist Public Adm and Justice, Hungary .
    Ward, Denise
    Forens Science South Australia, Australia .
    Willemse, Patricia
    Leiden University, Netherlands .
    P. H. Yap, Eric
    DSO National Labs, Singapore .
    Y. Y. Yong, Rita
    DSO National Labs, Singapore .
    Zupanic Pajnic, Irena
    University of Ljubljana, Slovenia .
    Kayser, Manfred
    Erasmus MC University, Netherlands .
    Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats2014In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 35, no 8, p. 1021-1032Article in journal (Refereed)
    Abstract [en]

    Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.

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  • 10.
    Beck, Olof
    et al.
    Karolinska Inst, Sweden.
    Ullah, Shahid
    Karolinska Inst, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    First evaluation of the possibility of testing for drugged driving using exhaled breath sampling2019In: Traffic Injury Prevention, ISSN 1538-9588, E-ISSN 1538-957X, Vol. 20, no 3, p. 238-243Article in journal (Refereed)
    Abstract [en]

    Objective: Driving under the influence of psychoactive drugs causes an increased risk for accidents. In combating this, sobriety tests at the roadside are common practice in most countries. Sampling of blood and urine for forensic investigation cannot be done at the roadside and poses practical problems associated with costs and time. An alternative specimen for roadside testing is therefore warranted and the aerosol particles in exhaled breath are one such alternative.Methods: The present study investigated how the exhaled breath sample compared with the routine legal investigations of blood and urine collected from suspects of drugged driving at 2 locations in Sweden. Exhaled breath was collected using a simple filter collection device and analyzed with state-of-the-art mass spectrometry technique.Results: The total number of cases used for this investigation was 67. In 54 of these cases (81%) the results regarding a positive or negative drug test result agreed and in 13 they disagreed. Out of these, the report from the forensic investigation of blood/urine was negative in 21 cases. In 6 of these, analytical findings were made in exhaled breath and these cases were dominated by the detection of amphetamine. In 7 cases a positive drug test from the forensic investigation was not observed in the breath sample and these cases were dominated by detection of tetrahydrocannabinol in blood. In total, 45 samples were positive with breath testing and the number of positives with established forensic methods was 46.Conclusion: The promising results from this study provide support to exhaled breath as a viable specimen for testing of drugged driving. The rapid, easy, and convenient sampling procedure offers the possibility to collect a drug test specimen at the roadside. The analytical investigation must be done in a laboratory at present because of the need for a highly sensitive instrument, which is already in use in forensic laboratories. The analytical work is not more challenging than for blood or oral fluid and should not cause an increase in cost. However, more studies need to be done before exhaled breath drug testing can be applied routinely for drugged driving investigation.

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  • 11.
    Benschop, Corina C G
    et al.
    Division of Biological Traces, Netherlands Forensic Institute.
    Connolly, Edward
    Forensic Science Ireland.
    Ansell, Ricky
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish National Forensic Centre, Linköping, Sweden.
    Kokshoorn, Bas
    Division of Biological Traces, Netherlands Forensic Institute.
    Results of an inter and intra laboratory exercise on the assessment of complex autosomal DNA profiles.2017In: Science & justice, ISSN 1355-0306, E-ISSN 1876-4452, Vol. 57, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    The interpretation of complex DNA profiles may differ between laboratories and reporting officers, which can lead to discrepancies in the final reports. In this study, we assessed the intra and inter laboratory variation in DNA mixture interpretation for three European ISO17025-accredited laboratories. To this aim, 26 reporting officers analyzed five sets of DNA profiles. Three main aspects were considered: 1) whether the mixed DNA profiles met the criteria for comparison to a reference profile, 2) the actual result of the comparison between references and DNA profiling data and 3) whether the weight of the DNA evidence could be assessed. Similarity in answers depended mostly on the complexity of the tasks. This study showed less variation within laboratories than between laboratories which could be the result of differences between internal laboratory guidelines and methods and tools available. Results show the profile types for which the three laboratories report differently, which informs indirectly on the complexity threshold the laboratories employ. Largest differences between laboratories were caused by the methods available to assess the weight of the DNA evidence. This exercise aids in training forensic scientists, refining laboratory guidelines and explaining differences between laboratories in court. Undertaking more collaborative exercises in future may stimulate dialog and consensus regarding interpretation. For training purposes, DNA profiles of the mixed stains and questioned references are made available.

  • 12.
    Boiso, Samuel
    et al.
    Swedish National Forensic Centre, Linköping, Sweden.
    Dalin, Erik
    Swedish National Forensic Centre, Linköping, Sweden.
    Seidlitz, Heidi
    Swedish National Forensic Centre, Linköping, Sweden.
    Sidstedt, Maja
    Swedish National Forensic Centre, Linköping, Sweden; Applied Microbiology, Department of Chemistry, Lund University, Lund, Sweden.
    Trygg, Elias
    Swedish National Forensic Centre, Linköping, Sweden.
    Hedman, Johannes
    Swedish National Forensic Centre, Linköping, Sweden; Applied Microbiology, Department of Chemistry, Lund University, Lund, Sweden.
    Ansell, Ricky
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish National Forensic Centre, Linköping, Sweden.
    RapidHIT for the purpose of stain analyses – An interrupted implementation2017In: Forensic Science International: Genetics Supplement Series, ISSN 1875-1768, E-ISSN 1875-175X, Vol. 6, no Supplement C, p. e589-e590Article in journal (Refereed)
    Abstract [en]

    Rapid DNA instruments have in recent years been developed, enabling analysis of forensic samples with a minimum of human intervention. Initially intended for fast handling of reference samples, such as samples from suspects in booking suites, attention shifted to include crime scene samples. The aim of this study was to determine whether or not the RapidHIT System (IntegenX) is fit for crime scene samples. The first runs gave very poor results, which was found to be due to an incorrect firmware setting leading to no or just minute amounts of amplicons being injected for electrophoresis. After solving this problem, 28 full runs (seven samples each) applying NGM SElect Express were performed comprising various amounts of blood on cotton swabs. Six of the runs failed completely, four due to cartridge leakage and in two runs the PCR mix was not injected. For 155 samples with 1–5ÎŒL blood (volumes for which complete DNA profiles are expected), 119 samples (77%) gave complete DNA profiles. Among the most serious failures were incorrect allele calling and leakage of DNA extract or PCR product. Other general issues were failure to export results, anode motor breakdown and broken capillary array. Due to the encountered problems with software, hardware and cartridges, together with the low success rate, it was decided not to continue towards implementation of the RapidHIT System in casework.

  • 13.
    Edston, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Dept Forens Med, Artillerigatan 12, S-58758 Linkoping, Sweden.
    Thymus Involution and Intravenous Drug Abuse2020In: American Journal of Forensic Medicine and Pathology, ISSN 0195-7910, E-ISSN 1533-404X, Vol. 41, no 1, p. 32-34Article in journal (Refereed)
    Abstract [en]

    Thymus glands from 283 autopsy cases were sampled and evaluated with histochemical and immunohistochemical methods. A subpopulation of 41 intravenous drug addicts were compared with age-matched control cases. It was found that an accelerated involution of the thymus occurred in the 20- to 25-year interval and thereafter with a steady pace of 5% per year. Also the size of Hassall bodies declined successively. In drug addicts, an increased dystrophic calcification of the Hassall bodies and a significant difference in thymus size (atrophy) compared with controls were seen. Moreover, a difference was seen in the relative numbers of CD4 and CD8 lymphocytes where CD4+ cells were reduced in drug addicts. It is hypothesized that signs of hepatitis C virus infection that was found in the majority of drug addicts and the reduced number of functionally intact Hassall corpuscles could explain the reduction of CD4+ lymphocytes and thymic hypotrophy in this population.

  • 14.
    Ekberg, Kerstin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Eklund, MonaInstitutionen för hälsovetenskaper, Arbetsterapi och aktivitetsvetenskap, Lunds universitet.Hensing, GunnelInstitutionen för medicin, Avd för samhällsmedicin och folkhälsa, Sahlgrenska akademien, Göteborgs universitet.
    Återgång i arbete: processer, bedömningar, åtgärder2015Collection (editor) (Other academic)
    Abstract [sv]

    Förmågan och möjligheten att arbeta är viktig både för den enskilda 
individen och för samhället. När en person helt eller delvis förlorar sin arbetsförmåga på grund av ohälsa ska olika aktörer i välfärds­samhället möjliggöra återgång i arbete. Sjukskrivnings- och rehabiliteringsprocessen blir i en del fall komplex beroende på variationer i aktörernas perspektiv på arbetsförmåga, de bedömningsmetoder som används och vilka regelverk som är tillämpbara. Kunskapsbaserade åtgärder för att främja återgång i arbete involverar i allmänhet arbetsplatsen som en central 
aktör och arena för åtgärder, medan praktiken ofta är annorlunda. 
Boken belyser förut­sättningar för att implementera kunskapsbaserade utredningar och åtgärder i det svenska samhället, liksom komplexiteten 
i dessa processer.

    Boken vänder sig till personer som arbetar med bedömning av arbetsförmåga och med åtgärder för att främja återgång i arbete. Målgrupper är studerande och professionella som i sin yrkesutövning inom till exempel primärvården, företagshälsovården eller inom privata rehabiliterings­enheter arbetar med sjukskrivningsprocesser och arbetslivsinriktad rehabilitering. Boken riktar sig också till arbetsgivare och arbetsledare som har ansvar för sjukskrivna medarbetares återgång i arbete.

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  • 15.
    Forsman, Asa
    et al.
    Swedish Natl Rd & Transport Res Inst VTI, SE-58195 Linkoping, Sweden.
    Anund, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Swedish Natl Rd & Transport Res Inst VTI, SE-58195 Linkoping, Sweden; Stockholm Univ, Sweden.
    Skyving, Marie
    Karolinska Inst, Sweden; Swedish Transport Agency, Sweden.
    Filtness, Ashleigh J.
    Loughborough Univ, England.
    Injury crashes and the relationship with disease causing excessive daytime sleepiness2021In: Traffic Injury Prevention, ISSN 1538-9588, E-ISSN 1538-957X, Vol. 22, no 4, p. 272-277Article in journal (Refereed)
    Abstract [en]

    Objective The objective of this study was to understand the relationship between some of the most common diseases that are known to contribute to excessive daytime sleepiness (EDS) and traffic injury crashes. Specific focus was on the relationship between disease and crash type (single-vehicle or multiple-vehicle crash) and between disease and injury severity. Methods This registry-based study considered all passenger car drivers involved in a crash in Sweden between 2011 and 2016 who were 40 years or older at the time of the crash (n = 54,090). For each crash-involved driver, selected medical diagnoses registered from 1997 until the day before the crash were extracted from the National Patient Register. The drivers were assigned to 1 of 4 groups, depending on prior diseases: sleep apnea (SA; group 1, n = 2,165), sleep disorders (group 2, n = 724), Parkinsons or epilepsy (group 3, n = 645) and a reference group (group 4, n = 50,556). Logistic regression analysis compared single-vehicle crashes with multiple-vehicle crashes and moderately/severely injured drivers with slightly/uninjured drivers. Results Drivers with EDS-related diseases (groups 1-3) had higher probability of a single-vehicle crash than a multiple-vehicle crash compared to the reference group. The most sizeable effect was found for Parkinsons/epilepsy with an odds ratio (OR) of 2.5 (confidence interval [CI], 2.1-3.0). For multiple-vehicle crashes, the probability of a moderate/severe injury was higher for drivers with other sleep disorders (OR = 1.5; CI, 1.0-2.2) and Parkinsons/epilepsy (OR = 1.6; CI, 1.1-2.3) compared to the reference group. Conclusions This study has made first steps toward understanding the relationship between some of the most common diseases that are known to contribute to EDS and crashes. Having Parkinsons/epilepsy, in particular, elevated the probability of a single-vehicle crash compared to a multiple-vehicle crash. A single-vehicle crash was seen as indicative of causing a crash; thus, having Parkinsons/epilepsy could be interpreted as a risk factor for crash involvement. Having Parkinsons/epilepsy, as well as other sleep disorders, was also related to more severe outcomes in multiple-vehicle crashes, given that a crash occurred. This was not identified in single-vehicle crashes.

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  • 16.
    Goldstein, Asher
    Linköping University, Department of Culture and Society, Division of Migration, Ethnicity and Society (REMESO). Linköping University, Faculty of Arts and Sciences.
    Flawed biometric rollouts in emerging economies: evidence from Jamaica, Afghanistan, and Kenya2022In: Breakthroughs in Digital Biometrics and Forensics / [ed] Kevin Daimi, Guillermo Francia III, Luis Hernández Encinas, Cham: Springer, 2022, p. 345-365Chapter in book (Refereed)
    Abstract [en]

    This chapter considers the social conditions in which large-scale biometric systems have been deployed in emerging economies across three cases: Jamaica, Afghanistan, and Kenya. Its contributions to the study of biometrics and forensics are both empirical and theoretical. The empirical contribution rests on the attention to comparatively under-researched geographies and political processes of technology-driven social transformation in the Caribbean, central Asia, and east Africa. The theoretical contribution rests on the elaboration of sociopolitical factors that have hampered the effective uptake of these technologies as well as engagement in dialogue with the body of literature on development-driven technological interventions into the governance of emerging economies. By undertaking a critical review of these contemporary cases, the chapter presents the state of the art in both theory and implementation while illustrating the necessities of popular legitimacy, equitable access, universal registration, and clearly elaborated data protection regimes in biometric rollouts.

  • 17.
    Grandell, Ida
    et al.
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, SE-58758 Linkoping, Sweden.
    Samara, Raed
    QIAGEN Science Inc, MD 21703 USA.
    Tillmar, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Artillerigatan 12, SE-58758 Linkoping, Sweden.
    A SNP panel for identity and kinship testing using massive parallel sequencing2016In: International journal of legal medicine, ISSN 0937-9827, E-ISSN 1437-1596, Vol. 130, no 4, p. 905-914Article in journal (Refereed)
    Abstract [en]

    Within forensic genetics, there is still a need for supplementary DNA marker typing in order to increase the power to solve cases for both identity testing and complex kinship issues. One major disadvantage with current capillary electrophoresis (CE) methods is the limitation in DNA marker multiplex capability. By utilizing massive parallel sequencing (MPS) technology, this capability can, however, be increased. We have designed a customized GeneRead DNASeq SNP panel (Qiagen) of 140 previously published autosomal forensically relevant identity SNPs for analysis using MPS. One single amplification step was followed by library preparation using the GeneRead Library Prep workflow (Qiagen). The sequencing was performed on a MiSeq System (Illumina), and the bioinformatic analyses were done using the software Biomedical Genomics Workbench (CLC Bio, Qiagen). Forty-nine individuals from a Swedish population were genotyped in order to establish genotype frequencies and to evaluate the performance of the assay. The analyses showed to have a balanced coverage among the included loci, and the heterozygous balance showed to have less than 0.5 % outliers. Analyses of dilution series of the 2800M Control DNA gave reproducible results down to 0.2 ng DNA input. In addition, typing of FTA samples and bone samples was performed with promising results. Further studies and optimizations are, however, required for a more detailed evaluation of the performance of degraded and PCR-inhibited forensic samples. In summary, the assay offers a straightforward sample-to-genotype workflow and could be useful to gain information in forensic casework, for both identity testing and in order to solve complex kinship issues.

  • 18.
    Guerrieri, Davide
    et al.
    National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Rapp, Emma
    National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Roman, Markus
    National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Thelander, Gunilla
    National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Acrylfentanyl: Another new psychoactive drug with fatal consequences2017In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 277, p. E21-E29Article in journal (Refereed)
    Abstract [en]

    The European Nordic Countries are the most exposed to opioid-related deaths. Between April and October 2016, a series of forty lethal intoxications occurred in Sweden, in which the presence of the synthetic opioid acrylfentanyl was determined to be the main - or a contributing - cause of death. In the reported cases, the blood concentration of acrylfentanyl - mostly detected in combination with other drugs - ranged from 0.01 ng/g to 5 ng/g; victims were predominantly males (34 males and 6 females), and their age varied between 18 and 53 years. We further describe five cases, representative of the different drug administration route (nasal spray, tablets) and intentions (accidental or voluntary intoxication). Moreover, we address nine cases of non-lethal intoxication, in single (8 cases) or polydrug scenario (1 case). We discuss the present characteristics of the Swedish drug market for fentanyl-analogs in general and acrylfentanyl in particular, reporting a structural difficulty to effectively counteracting the appearance of unscheduled substances due to the constant turnover of new molecules on the recreational drug market. (C) 2017 Published by Elsevier Ireland Ltd.

  • 19.
    Gundersen, Per Ole M.
    et al.
    St Olavs Univ Hosp, Norway; Norwegian Univ Sci and Technol, Norway.
    Broecker, Sebastian
    Broeckers Solut, Germany.
    Slordal, Lars
    St Olavs Univ Hosp, Norway; Norwegian Univ Sci and Technol, Norway.
    Spigset, Olav
    St Olavs Univ Hosp, Norway; Norwegian Univ Sci and Technol, Norway.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Natl Forens Ctr, Drug Unit, Linkoping, Sweden.
    Retrospective screening of synthetic cannabinoids, synthetic opioids and designer benzodiazepines in data files from forensic post mortem samples analysed by UHPLC-QTOF-MS from 2014 to 20182020In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 311, article id 110274Article in journal (Refereed)
    Abstract [en]

    The introduction of new psychoactive substances (NPS) on the illicit drug market has led to major challenges for the analytical laboratories. Keeping screening methods up to date with all relevant drugs is hard to achieve and the risk of missing important findings in biological samples is a matter of concern. Aiming for an extended retrospective data analysis, diagnostic fragment ions from synthetic cannabinoids (n = 251), synthetic opioids (n = 88) and designer benzodiazepines (n = 26) not included in our original analytical method were obtained from the crowdsourced database HighResNPS.com and converted to a personalized library in a format compatible with the analytical instrumentation. Data files from the analysis of 1314 forensic post mortem samples with an Agilent 6540 ultra high pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) performed in our laboratory from January 2014 to December 2018 were retrieved and retrospectively processed with the new personalized library. Potentially positive findings were grouped in two: The most confident findings contained MS/MS data for library match (category 1) whereas the less confident findings lacked such data (category 2). Five new category 1 findings were identified: Flubromazepam in two data files from 2015 and 2016, respectively, phenibut (4-amino-3-phenylbutyric acid) in one data file from 2015, fluorofentanyl in one data file from 2016 and cyclopropylfentanyl in one data file from 2018. Retention time matches with reference standards further strengthened these findings. A list of 35 presumably positive category 2 findings was generated. Of these, only one finding of phenibut was considered plausible after checking retention times and signal-to-noise ratios. This study shows that new compounds can be detected retrospectively in data files from QTOF-MS using an updated library containing diagnostic fragment ions. Automatic screening procedures can be useful, but a manual re-evaluation of positive findings will always be necessary. (C) 2020 The Author(s). Published by Elsevier B.V.

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  • 20. Order onlineBuy this publication >>
    Haage, Pernilla
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Forensic Toxicological Aspects of Tramadol: Focus on Enantioselective Drug Disposition and Pharmacogenetics2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    One of the most difficult parts in forensic toxicology is to interpret obtained drug concentrations. Was it therapeutic, toxic or even lethal to the particular individual that the blood sample was drawn from? Concentrations of opioid drugs are especially difficult to interpret, because of large interindividual differences in innate and acquired tolerance.

    Tramadol is a complex drug. Not only is it an opioid, it is also a racemic drug with the (+)- and (-)-enantiomers of the parent compound and metabolites showing different pharmacological effects. Further, it is metabolized by polymorphic enzymes, which may affect the amounts of metabolites formed and possibly the enantiomer ratios of the parent compound and its metabolites. It has been speculated that particularly the (+)/(-)-enantiomer ratio of O-desmethyltramadol is related to the risk of adverse effects, and it has been shown that the ratio is affected by CYP2D6 genotype.

    The overall aim of the thesis was to evaluate if forensic interpretations of tramadol, regarding toxicity and time since drug administration, may be improved by the use of genotyping and enantioselective concentration determination of tramadol and its three main metabolites.

    To simultaneously quantify the enantiomer concentrations of tramadol, Odesmethyltramadol, N-desmethyltramadol and N,O-didesmethyltramadol in whole blood, a liquid chromatography tandem mass spectrometry (LCMS/MS) method was developed and validated. Genetic variation in CYP2D6, CYP2B6, CYP3A4 (encoding the tramadol metabolizing enzymes), ABCB1 (encoding a transport protein) and OPRM1 (encoding the μ-opioid receptor) was investigated, using pyrosequencing, xTAG, and TaqMan analysis. The methods were applied to the blood samples of two study populations; 19 healthy volunteers administered a therapeutic, single tramadol dose, and 159 tramadol positive autopsy cases.

    The most important finding was the positive correlations between all four enantiomer ratios and time since tramadol administration in the healthy volunteers. All enantiomer ratios except the one of tramadol was also affected by the CYP2D6 genotype, which was apparent among the autopsy cases as well. Genetic variation in CYP2D6 and possibly CYP2B6 was shown to have an impact on tramadol pharmacokinetics, although no association to neither drug related symptoms nor tramadol related causes of death was found. Tramadol intoxications were predominantly characterized by low age (median 26 years) and male sex, often with a history of substance abuse and with other drugs (at fairly low concentrations) detected in blood.

    In conclusion, enantiomer concentration determination combined with genotyping seems promising regarding estimations of time since drug administration, although is of low value concerning interpretations of toxicity in autopsy cases.

    List of papers
    1. Pharmacogenetic aspects of tramadol pharmacokinetics and pharmacodynamics after a single oral dose
    Open this publication in new window or tab >>Pharmacogenetic aspects of tramadol pharmacokinetics and pharmacodynamics after a single oral dose
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    2014 (English)In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 238, p. 125-132Article in journal (Refereed) Published
    Abstract [en]

    The major purpose of this study was to elucidate if genotyping can facilitate interpretations of tramadol (TRA) in forensic case work, with special regard to the estimation of the time of drug intake and drug related symptoms (DRS). The association between genetic polymorphisms in CYP2D6, OPRM1 and ABCB1 and pharmacokinetic and pharmacodynamic properties of TRA was studied. Nineteen healthy volunteers were randomized into two groups receiving a single dose of either 50 or 100 mg of orally administrated TRA. Blood samples were collected prior to dosing and up to 72 h after drug intake. The subjects were asked to report DRS during the experimental day. We found a positive correlation between the metabolic ratio of O-desmethyltramadol (ODT) to TRA and the time after drug intake for both CYP2D6 intermediate metabolizers and extensive metabolizers. For the only poor metabolizer with detectable ODT levels the metabolic ratio was almost constant. Significant associations were found between the area under the concentration-time curve (AUC) and three of the investigated ABCB1 single nucleotide polymorphisms for TRA, but not for ODT and only in the 50 mg dosage group. There was great interindividual variation in DRS, some subjects exhibited no symptoms at all whereas one subject both fainted and vomited after a single therapeutic dose. However, no associations could be found between DRS and investigated polymorphisms. We conclude that the metabolic ratio of ODT/TRA may be used for estimation of the time of drug intake, but only when the CYP2D6 genotype is known and taken into consideration. The influence of genetic polymorphisms in ABCB1 and OPRM1 requires further study.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Tramadol; Pharmacokinetics; Pharmacodynamics; CYP2D6; ABCB1; OPRM1
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106838 (URN)10.1016/j.forsciint.2014.03.003 (DOI)000334580700025 ()24709712 (PubMedID)
    Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2020-08-18Bibliographically approved
    2. Quantitation of the enantiomers of tramadol and its three main metabolites in human whole blood using LC-MS/MS.
    Open this publication in new window or tab >>Quantitation of the enantiomers of tramadol and its three main metabolites in human whole blood using LC-MS/MS.
    2016 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 119, p. 1-9Article in journal (Refereed) Published
    Abstract [en]

    The analgesic drug tramadol and its metabolites are chiral compounds, with the (+)- and (-)-enantiomers showing different pharmacological and toxicological effects. This novel enantioselective method, based on LC-MS/MS in reversed phase mode, enabled measurement of the parent compound and its three main metabolites O-desmethyltramadol, N-desmethyltramadol and N,O-didesmethyltramadol simultaneously. Whole blood samples of 0.5g were fortified with internal standards (tramadol-(13)C-D3 and O-desmethyl-cis-tramadol-D6) and extracted under basic conditions (pH 11) by liquid-liquid extraction. Chromatography was performed on a chiral alpha-1-acid glycoprotein (AGP) column preceded by an AGP guard column. The mobile phase consisted of 0.8% acetonitrile and 99.2% ammonium acetate (20mM, pH 7.2). A post-column infusion with 0.05% formic acid in acetonitrile was used to enhance sensitivity. Quantitation as well as enantiomeric ratio measurements were covered by quality controls. Validation parameters for all eight enantiomers included selectivity (high), matrix effects (no ion suppression/enhancement), calibration model (linear, weight 1/X(2), in the range of 0.25-250ng/g), limit of quantitation (0.125-0.50ng/g), repeatability (2-6%) and intermediate precision (2-7%), accuracy (83-114%), dilution integrity (98-115%), carry over (not exceeding 0.07%) and stability (stable in blood and extract). The method was applied to blood samples from a healthy volunteer administrated a single 100mg dose and to a case sample concerning an impaired driver, which confirmed its applicability in human pharmacokinetic studies as well as in toxicological and forensic investigations.

    Keywords
    Enantiomer; LC–MS/MS; N, O-didesmethyltramadol; N-desmethyltramadol; O-desmethyltramadol; Tramadol
    National Category
    Analytical Chemistry
    Identifiers
    urn:nbn:se:liu:diva-125284 (URN)10.1016/j.jpba.2015.11.012 (DOI)000370211900001 ()26625281 (PubMedID)
    Note

    Funding agencies:The National Board of Forensic Medicine in Sweden funded this work.

    Available from: 2016-02-19 Created: 2016-02-19 Last updated: 2020-08-18
    3. Enantioselective pharmacokinetics of tramadol and its three main metabolites; impact of CYP2D6, CYP2B6, and CYP3A4 genotype
    Open this publication in new window or tab >>Enantioselective pharmacokinetics of tramadol and its three main metabolites; impact of CYP2D6, CYP2B6, and CYP3A4 genotype
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    2018 (English)In: Pharmacology Research & Perspectives, E-ISSN 2052-1707, Vol. 6, no 4, article id e00419Article in journal (Refereed) Published
    Abstract [en]

    Tramadol is a complex drug, being metabolized by polymorphic enzymes and administered as a racemate with the (+)- and (-)-enantiomers of the parent compound and metabolites showing different pharmacological effects. The study aimed to simultaneously determine the enantiomer concentrations of tramadol, O-desmethyltramadol, N-desmethyltramadol, and N,O-didesmethyltramadol following a single dose, and elucidate if enantioselective pharmacokinetics is associated with the time following drug intake and if interindividual differences may be genetically explained. Nineteen healthy volunteers were orally administered either 50 or 100 mg tramadol, whereupon blood samples were drawn at 17 occasions. Enantiomer concentrations in whole blood were measured by LC-MS/MS and the CYP2D6,CYP2B6 and CYP3A4 genotype were determined, using the xTAG CYP2D6 Kit, pyrosequencing and real-time PCR, respectively. A positive correlation between the (+)/(-)-enantiomer ratio and time following drug administration was shown for all four enantiomer pairs. The largest increase in enantiomer ratio was observed for N-desmethyltramadol in CYP2D6 extensive and intermediate metabolizers, rising from about two to almost seven during 24 hours following drug intake. CYP2D6 poor metabolizers showed metabolic profiles markedly different from the ones of intermediate and extensive metabolizers, with large area under the concentration curves (AUCs) of the N-desmethyltramadol enantiomers and low corresponding values of the O-desmethyltramadol and N,O-didesmethyltramadol enantiomers, especially of the (+)-enantiomers. Homozygosity of CYP2B6 *5 and *6 indicated a reduced enzyme function, although further studies are required to confirm it. In conclusion, the increase in enantiomer ratios over time might possibly be used to distinguish a recent tramadol intake from a past one. It also implies that, even though (+)-O-desmethyltramadol is regarded the enantiomer most potent in causing adverse effects, one should not investigate the (+)/(-)-enantiomer ratio of O-desmethyltramadol in relation to side effects without consideration for the time that has passed since drug intake.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2018
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:liu:diva-152586 (URN)10.1002/prp2.419 (DOI)000442994300006 ()29992026 (PubMedID)2-s2.0-85052511964 (Scopus ID)
    Available from: 2018-11-09 Created: 2018-11-09 Last updated: 2021-07-01Bibliographically approved
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    Forensic Toxicological Aspects of Tramadol: Focus on Enantioselective Drug Disposition and Pharmacogenetics
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  • 21.
    Hoiseth, G.
    et al.
    Oslo Univ Hosp, Norway; Diakonhjemmet Hosp, Norway; Univ Oslo, Norway.
    Nilsson, G. H.
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Lundberg, R.
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Forsman, M.
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Kronstrand, C
    Linköping University, Faculty of Medicine and Health Sciences.
    Nystrom, I
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Oscarsson, C.
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Ericsson, E.
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Cherma, M. D.
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Evaluating the hip-flask defence using analytical data from ethanol and ethyl glucuronide. A comparison of two models2020In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 316, article id 110409Article in journal (Refereed)
    Abstract [en]

    Aim: Claimed intake of alcohol after a traffic incident, called the hip-flask defence, can be objectively assessed by different methods. One of them is the use of two consecutive ethanol concentrations in urine and the ratio between ethanol concentrations in urine and blood. Another one is the concentrations of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in blood and their ratio to ethanol. The experimental basis for both these models is from single dose studies only. The aim of this study was therefore to describe the kinetics of ethanol, EtG and EtS after ingestion of two repeated doses of ethanol and to investigate the usefulness of the different models for the assessment of the hip-flask defence. Methods: Thirty-five subjects ingested a first dose of 0.51 g of ethanol per kilo body weight, and two hours later a second dose (the hip-flask drink) of 0.25, 0.51 or 0.85 g of ethanol per kilo body weight. Ten urine and 17 blood samples were collected and analysed for ethanol, EtG and EtS using fully validated methods. It was investigated if all subjects fulfilled the criteria for recent drinking, according to the two different models, when using the samples collected 180-240 minutes after start of first dose drinking. According to the first model, increase in urinary ethanol concentrations and a ratio UAC/BAC below 1.3 indicated recent drinking. According to the second model, increase in blood EtG concentrations and a ratio ethanol (g/kg)/EtG (mg/L) above 1 indicated recent drinking. Results: All subjects in the high dose group fulfilled all criteria for recent drinking. One subject in the medium dose group and nine subjects in the low dose group failed to show increasing UAC and/or a UAC/ BAC ratio below 1.3. One subject in the low dose group failed to show increasing concentrations of blood EtG, but all subjects showed a ratio ethanol/EtG above 1. Conclusions: The present study showed, by the use of experimental data, that both two models used to investigate the hip-flask defence can be used, but only when the hip-flask dose is sufficiently high. (C) 2020 The Author(s). Published by Elsevier B.V.

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  • 22.
    Jackowski, Christian
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Center for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Bern, Switzerland.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology.
    Thali, Michael J.
    Center for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Bern, Switzerland.
    Whole body postmortem angiography with a high viscosity contrast agent solution using poly ethylene glycol as contrast agent dissolver2008In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 53, no 2, p. 465-468Article in journal (Refereed)
    Abstract [en]

    Postmortem minimal invasive angiography has already been implemented to support virtual autopsy examinations. An experimental approach in a porcine model to overcome an initially described artificial tissue edema artifact by using a poly ethylene glycol (PEG) containing contrast agent solution showed promising results. The present publication describes the first application of PEG in a whole corpse angiographic CT examination. A minimal invasive postmortem CT angiography was performed in a human corpse utilizing the high viscosity contrast agent solution containing 65% of PEG. Injection was carried out via the femoral artery into the aortic root in simulated cardiac output conditions. Subsequent CT scanning delivered the 3D volume data of the whole corpse. Visualization of the human arterial anatomy was excellent and the contrast agent distribution was generally limited to the arterial system as intended. As exceptions an enhancement of the brain, the left ventricular myocardium and the renal cortex became obvious. This most likely represented the stage of centralization of the blood circulation at the time of death with dilatation of the precapillary arterioles within these tissues. Especially for the brain this resulted in a distinctively improved visualization of the intracerebral structures by CT. However, the general tissue edema artifact of postmortem minimal invasive angiography examinations could be distinctively reduced. © 2008 American Academy of Forensic Sciences.

  • 23. Order onlineBuy this publication >>
    Jakobsson, Gerd
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Oxycodone in Forensic Toxicology: Analytical Strategies and Interpretation2022Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Oxycodone is a common finding in forensic casework and widely used as an analgetic. Oxycodone’s pharmacokinetic and pharmacodynamic properties make the interpretation of post mortem oxycodone blood concentrations complicated. Coadministered substances and inter-individual differences in metabolic capacity can alter the oxycodone blood concentration and thereby cause an unexpected pharmacological effect and possibly lead to negative side-effects, respiratory depression, and death. As the level of tolerance often is unknown in post mortem cases the correlation between blood concentration and effect is weak. In this thesis, the overall aim was to increase the ability to determine cause and manner of death in suspected oxycodone intoxications, by studying concentrations of oxycodone and its metabolites, CYP2D6 phenotype, as well as endogenous substances in post mortem cases. Moreover, trends and patterns in prescription and post mortem findings of substances causing pharmacodynamic and pharmacokinetic interactions with oxycodone were studied.

    In paper I, concentrations of oxycodone, noroxycodone, oxymorphone and noroxymorphone were determined in femoral blood from 192 post mortem cases by LC-MS/MS. Concentrations and the metabolite-to-parent drug ratio were studied in groups separated by cause of death, A) intoxication by oxycodone, B) intoxication caused by oxycodone and additional substance/s, C) intoxication where oxycodone did not contribute, D) other causes of death than intoxication. It was found that concentrations above 0.2 μg/g indicate an oxycodone intoxication but that concentrations up to 0.3 μg/g can be seen in tolerant individuals. The results also demonstrated that a low noroxycodone/oxycodone ratio indicates an oxycodone intoxication. Paper II included LC-MS/MS analysis as in paper I, and in addition, genotyping for CYP2D6 enzyme activity in 174 cases. The metabolite-to-parent drug ratios were compared between poor, intermediate, extensive, and ultra-rapid metabolizers. It was concluded that with knowledge of CYP2D6 activity the oxymorphone/oxycodone ratio could distinguish between oxycodone-related deaths and other causes of deaths. Paper III was a pharmacoepidemiological study where post mortem findings were investigated in combination with prescription records in 1081 cases to evaluate the presence of interacting drugs in oxycodone-related intoxications. One of the main findings was that pharmacodynamically interacting drugs were twice as often prescribed, and five times more common as a co-finding in oxycodone-related intoxications compared to other causes of death. An oxycodone prescription was missing in 34% of all cases, with a trend that individuals, 35 years or below, more often lacked an oxycodone prescription. In paper IV, the post mortem metabolome was explored in 934 cases to reveal possible biomarkers correlated with oxycodone intoxications. The results showed that levels of acylcarnitines, a group of endogenous substances involved in mitochondrial metabolism, were significantly decreased in oxycodone-related intoxications compared to a control group, revealing post mortem metabolome analysis as a possible complemental approach of interpretation in post mortem toxicology.

    In conclusion, this thesis emphasizes the importance of including metabolites in the toxicological analytical strategy to improve the interpretation in post mortem case work. Also, the applicability of pharmacogenetic analysis is highly useful in certain cases. Furthermore, the use of post mortem metabolomics is a possible future promising strategy to the early identification of oxycodone-related deaths.

    List of papers
    1. Oxycodone Concentrations and Metabolic Ratios in Femoral Blood from Fatal Intoxications and Other Causes of Death using LC-MS-MS
    Open this publication in new window or tab >>Oxycodone Concentrations and Metabolic Ratios in Femoral Blood from Fatal Intoxications and Other Causes of Death using LC-MS-MS
    2021 (English)In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 45, no 2, p. 124-133Article in journal (Refereed) Published
    Abstract [en]

    Oxycodone (OC) is an opioid with strong analgesic effects widely used to treat acute and chronic pain. Interpretation of OC concentrations in postmortem cases is complicated due to tolerance and overlapping concentrations for fatal and non-fatal levels. In this study, our aim was to develop and validate a method for OC and its three metabolites: noroxycodone (NOC), oxymorphone (OM) and noroxymorphone (NOM) in postmortem femoral blood. Our goal was to define reference concentrations for intoxications and non-intoxications and investigate metabolic ratios in different causes of death. A rapid LC-MS-MS method using protein-precipitated postmortem blood was developed. Lower limit of quantitation was 0.005 mu g/g blood for all analytes; upper limit of quantitation was 1.0 mu g/g for OC and NOC and 0.25 mu g/g for OM and NOM. The method displayed high precision (3.3-7.7%) and low bias (-0.3 to 12%). In total, 192 cases were analyzed and concentrations ranged from 0.005 to 13 mu g/g for OC, 0.005 to 2.0 mu g/g for NOC, 0.005 to 0.24 mu g/g for OM, and 0.005 to 0.075 mu g/g for NOM. We found a significant difference in OC concentration between the cases where OC contributed and those where it did not. In spite of that, we do not recommend the use of a specific blood concentration to distinguish fatal intoxications. Instead, the percentiles from our data set suggest that concentrations >0.2 mu g/g are likely to have contributed to toxicity, but that concentrations as high as 0.3 might be tolerated without toxic effects. In addition, we also found that a low NOC/OC ratio could point toward an acute fatal intoxication. In conclusion, the OC concentration alone may not be sufficient to diagnose a fatal intoxication.

    Place, publisher, year, edition, pages
    OXFORD UNIV PRESS INC, 2021
    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:liu:diva-176204 (URN)10.1093/jat/bkaa051 (DOI)000650099000005 ()32435814 (PubMedID)
    Note

    Funding Agencies|Strategic Research Area of Forensic Science at Linkoping University, Sweden [2017-8]; National Board of Forensic Medicine in Sweden

    Available from: 2021-06-09 Created: 2021-06-09 Last updated: 2022-09-13
    2. Oxycodone findings and CYP2D6 function in postmortem cases
    Open this publication in new window or tab >>Oxycodone findings and CYP2D6 function in postmortem cases
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    2021 (English)In: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 53, article id 102510Article in journal (Refereed) Published
    Abstract [en]

    Genetic disposition can cause variation in oxycodone pharmacokinetic characteristics and decrease or increase the expected clinical response. In forensic medicine, determination of cause of death or assessing time between drug intake and death can be facilitated by knowledge of parent and metabolite concentrations. In this study, the aim was to investigate if CYP2D6 genotyping can facilitate interpretation by investigating the frequency of the four CYP2D6 phenotypes, poor metabolizer, intermediate metabolizer, extensive metabolizer, and ultra-rapid metabolizer in postmortem cases, and to study if the CYP2D6 activity was associated with a certain cause of death, concentration, or metabolic ratio. Cases positive for oxycodone in femoral blood (n = 174) were genotyped by pyrosequencing for CYP2D6*3, *4, and *6 and concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were determined by LC-MS/MS (LLOQ 0.005 mu g/g). Digital droplet PCR was used to determine the copy number variation for CYP2D6*5. Cases were categorized by cause of death. It was found that poor and intermediate CYP2D6 metabolizers had significantly higher oxycodone and noroxycodone concentrations compared to extensive and ultra-rapid metabolizers. CYP2D6 phenotype were equally distributed between cause of death groups, showing that no phenotype was overrepresented in any of the cause of death groups. We also found that the concentration ratio between oxymorphone and oxycodone depended on the CYP2D6 activity when death was unrelated to intoxication. In general, a low metabolite to parent ratio indicate an acute intake. By using receiver operating characteristic (ROC) analysis, we conclude that an oxymorphone/ oxycodone ratio lower than 0.075 has a high sensitivity for separating intoxications with oxycodone from other intoxications and non-intoxications. However, the phenotype needs to be known to reach a high specificity. Therefore, the ratio should not be used as a biomarker on its own to distinguish between different causes of death but needs to be complemented by genotyping.

    Place, publisher, year, edition, pages
    ELSEVIER IRELAND LTD, 2021
    Keywords
    Oxycodone related deaths; Pharmacogenetics; Postmortem toxicology; Metabolite ratios; Forensic Toxicology
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:liu:diva-178431 (URN)10.1016/j.fsigen.2021.102510 (DOI)000674512400008 ()33799050 (PubMedID)
    Note

    Funding Agencies|Strategic Research Area of Forensic Science at Linkoping University, Sweden [2017-8]; National Board of Forensic Medicine in Sweden

    Available from: 2021-08-26 Created: 2021-08-26 Last updated: 2022-09-13
    3. Oxycodone-Related Deaths: The Significance of Pharmacokinetic and Pharmacodynamic Drug Interactions
    Open this publication in new window or tab >>Oxycodone-Related Deaths: The Significance of Pharmacokinetic and Pharmacodynamic Drug Interactions
    Show others...
    2022 (English)In: European journal of drug metabolism and pharmacokinetics, ISSN 0378-7966, E-ISSN 2107-0180, Vol. 47, p. 259-270Article in journal (Refereed) Published
    Abstract [en]

    Background and Objectives Oxycodone is frequently prescribed as well as detected in postmortem cases. Concurrent use of pharmacodynamically or pharmacokinetically interacting drugs can cause adverse effects or even fatal intoxication. The aims of this study were to investigate differences in prescriptions for and toxicological findings of pharmacodynamically and pharmacokinetically interacting drugs in fatal oxycodone-related intoxications and other causes of death. We also aimed to investigate the differences in prevalence of oxycodone prescriptions, and the detected postmortem oxycodone concentrations between fatal oxycodone-related intoxications and other causes of death. Methods Forensic autopsy cases (2012-2018) where oxycodone was identified in femoral blood (n = 1236) were included. Medical history and prescription data were retrieved from national databases and linked to the forensic toxicology findings. Results Oxycodone-related deaths were found to have higher blood concentrations of oxycodone (median 0.30 mu g/g vs. 0.05 mu g/g) and were less likely to have a prescription for oxycodone (OR 0.62) compared to nonintoxication deaths. Pharmacodynamically interacting drugs were prescribed in 79% and found in blood in 81% of the cases. Pharmacokinetically interacting drugs were rarely prescribed (1%). Oxycodone-related deaths were more likely to have prescriptions for a pharmacodynamically interacting drug (OR 1.7) and more often have co-findings of one or multiple pharmacodynamically interacting drugs (OR 5.6). Conclusion The results suggest that combined use of oxycodone and pharmacodynamically interacting drugs is associated with oxycodone-related death and that non-medical use of oxycodone is a potential risk factor for oxycodone-related intoxication.

    Place, publisher, year, edition, pages
    Springer France, 2022
    National Category
    Forensic Science
    Identifiers
    urn:nbn:se:liu:diva-182500 (URN)10.1007/s13318-021-00750-9 (DOI)000742261600001 ()35025054 (PubMedID)
    Note

    Funding Agencies|National Board of Forensic Medicine

    Available from: 2022-01-26 Created: 2022-01-26 Last updated: 2023-03-10Bibliographically approved
    4. Postmortem Metabolomics Reveal Acylcarnitines as Potential Biomarkers for Fatal Oxycodone-Related Intoxication
    Open this publication in new window or tab >>Postmortem Metabolomics Reveal Acylcarnitines as Potential Biomarkers for Fatal Oxycodone-Related Intoxication
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    2022 (English)In: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 12, no 2, article id 109Article in journal (Refereed) Published
    Abstract [en]

    Postmortem metabolomics has recently been suggested as a potential tool for discovering new biological markers able to assist in death investigations. Interpretation of oxycodone concentrations in postmortem cases is complicated, as oxycodone tolerance leads to overlapping concentrations for oxycodone intoxications versus non-intoxications. The primary aim of this study was to use postmortem metabolomics to identify potential endogenous biomarkers that discriminate between oxycodone-related intoxications and non-intoxications. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry data from 934 postmortem femoral blood samples, including oxycodone intoxications and controls positive and negative for oxycodone, were used in this study. Data were processed and evaluated with XCMS and SIMCA. A clear trend in group separation was observed between intoxications and controls, with a model sensitivity and specificity of 80% and 76%. Approximately halved levels of short-, medium-, and long-chain acylcarnitines were observed for oxycodone intoxications in comparison with controls (p < 0.001). These biochemical changes seem to relate to the toxicological effects of oxycodone and potentially acylcarnitines constituting a biologically relevant biomarker for opioid poisonings. More studies are needed in order to elucidate the potential of acylcarnitines as biomarker for oxycodone toxicity and their relation to CNS-depressant effects.

    Place, publisher, year, edition, pages
    MDPI, 2022
    Keywords
    metabolomics; biomarkers; postmortem; acylcarnitine; death investigation; forensic sciences; beta-oxidation; oxycodone; opioids
    National Category
    Bioinformatics and Systems Biology
    Identifiers
    urn:nbn:se:liu:diva-184274 (URN)10.3390/metabo12020109 (DOI)000774234800001 ()35208184 (PubMedID)
    Available from: 2022-04-12 Created: 2022-04-12 Last updated: 2022-09-13
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  • 24.
    Jakobsson, Gerd
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Gustavsson, Sara
    Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Jönsson, Anna K.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Gréen, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Oxycodone-Related Deaths: The Significance of Pharmacokinetic and Pharmacodynamic Drug Interactions2022In: European journal of drug metabolism and pharmacokinetics, ISSN 0378-7966, E-ISSN 2107-0180, Vol. 47, p. 259-270Article in journal (Refereed)
    Abstract [en]

    Background and Objectives Oxycodone is frequently prescribed as well as detected in postmortem cases. Concurrent use of pharmacodynamically or pharmacokinetically interacting drugs can cause adverse effects or even fatal intoxication. The aims of this study were to investigate differences in prescriptions for and toxicological findings of pharmacodynamically and pharmacokinetically interacting drugs in fatal oxycodone-related intoxications and other causes of death. We also aimed to investigate the differences in prevalence of oxycodone prescriptions, and the detected postmortem oxycodone concentrations between fatal oxycodone-related intoxications and other causes of death. Methods Forensic autopsy cases (2012-2018) where oxycodone was identified in femoral blood (n = 1236) were included. Medical history and prescription data were retrieved from national databases and linked to the forensic toxicology findings. Results Oxycodone-related deaths were found to have higher blood concentrations of oxycodone (median 0.30 mu g/g vs. 0.05 mu g/g) and were less likely to have a prescription for oxycodone (OR 0.62) compared to nonintoxication deaths. Pharmacodynamically interacting drugs were prescribed in 79% and found in blood in 81% of the cases. Pharmacokinetically interacting drugs were rarely prescribed (1%). Oxycodone-related deaths were more likely to have prescriptions for a pharmacodynamically interacting drug (OR 1.7) and more often have co-findings of one or multiple pharmacodynamically interacting drugs (OR 5.6). Conclusion The results suggest that combined use of oxycodone and pharmacodynamically interacting drugs is associated with oxycodone-related death and that non-medical use of oxycodone is a potential risk factor for oxycodone-related intoxication.

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  • 25.
    Johansson, Anna
    et al.
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Lindstedt, Daniel
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Roman, Markus
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Thelander, Gunilla
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Nielsen, Elisabet I.
    Uppsala University, Sweden.
    Lennborn, Ulrica
    Uppsala University, Sweden.
    Sandler, Hakan
    National Board Forens Med, Sweden; Uppsala University, Sweden.
    Rubertsson, Sten
    Uppsala University, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP2017In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 275, p. 76-82Article in journal (Refereed)
    Abstract [en]

    Introduction: 3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016. Case descriptions: The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22 h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse. Methods: 3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry. Results: In the clinical case, the concentration of 3-MeO-PCP was 0.14 mu g/g at admission, 0.08 mu g/g 2.5 h after admission, 0.06 mu g/g 5 h after admission and 0.04 mu g/g 17 h after admission. The half-life of 3-MeO-PCP was estimated to 11 h. In the autopsy cases, femoral blood concentrations ranged from 0.05 mu g/g to 0.38 mu g/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well. Conclusion: Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment. (C) 2017 Elsevier B. V. All rights reserved.

  • 26.
    Jones, A Wayne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Highly cited forensic practitioners in the discipline legal and forensic medicine and the importance of peer-review and publication for admission of expert testimony2022In: Forensic Science, Medicine, and Pathology, ISSN 1547-769X, E-ISSN 1556-2891, Vol. 18, no 1, p. 37-44Article in journal (Refereed)
    Abstract [en]

    Peer-review of manuscripts submitted to scholarly journals for publication dates back similar to 350 years and this process represents the foundation of scientific publishing. After a manuscript has undergone and survived a rigorous peer-review, this conveys a stamp of approval, because it signifies the work has been checked by independent experts in the scientific discipline concerned. The publication and citation track records of people instructed to appear as expert witness in civil and criminal litigation are important considerations. Using a publically available database, the most highly cited scientists in the discipline legal and forensic medicine were identified. For each scientist, a composite score was calculated based on six different citation metrics; (i) Total number of citations, (ii) H-index, (iii) H-m-index, which modifies the H-index for multi-authored papers, (iv) Citations to single-author papers, (v) Citations to single and first author papers and (vi) citations to single, first and last author papers. The top 100,000 most highly cited scientists from all disciplines were identified along with the top 2% of the most highly cited in each of 176 sub-fields. The latest version of the citation databases, up to the end of 2020, classified 14.163 people as having legal and forensic medicine as their primary research discipline. Of these, there were 29 names listed among the top 100,000 most highly cited in all disciplines and 299 were among the top cited 2% in their particular sub-field. More than 50% of the highly cited forensic practitioners resided in four countries (USA, Germany, UK and Australia). The top-ten most highly cited individuals were the same in all four versions of the database (2017, 2018, 2019 and 2020) and represented the sub-disciplines of toxicology (n = 3), genetics/DNA/heredity (n = 3), whereas two specialized in pathology/toxicology and two in pathology/genetics.

  • 27.
    Jones, A Wayne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Insulin murder and the case of Colin Norris2023In: Journal of Forensic and Legal Medicine, ISSN 1752-928X, E-ISSN 1878-7487, Vol. 94, article id 102483Article, review/survey (Refereed)
    Abstract [en]

    Although insulin is an essential medicine and a life-saving drug, it has also been incriminated in many poisoning deaths; accidental, suicidal and some with malicious intent. Overdosing with insulin precipitates a lifethreatening state of hypoglycemia and if untreated leads to coma, irreversible brain damage and death. Normally, the pancreatic 13-cells secrete equimolar amounts of insulin and C-peptide into the portal venous blood, although under physiological conditions the plasma concentration ratio (insulin/C-peptide) is less than unity, because insulin is more susceptible to hepatic first-pass metabolism. A high ratio of insulin/C-peptide in plasma from a poisoned patient is compelling evidence that pharmaceutical insulin was administered, which does not contain C-peptide. The analysis of insulin and C-peptide was traditionally done by immunoassay methods (RIA and/or ELISA), although high resolution LC-MS/MS is more suitable for forensic purposes and permits the identification of insulin analogues. Use of insulin as a murder weapon is exemplified by the case of Colin Norris, a male nurse found guilty of murdering four elderly patients and the attempted murder of a fifth by injecting them with insulin. However, the prosecution evidence against Norris was mainly circumstantial and hearsay. Toxicological evidence against Norris consisted of a high insulin/C-peptide concentration ratio in plasma from one of the victims. This analysis was done by an immunoassay method at a clinical laboratory and not a forensic laboratory. Analytical procedures, including chain-of-custody routines, are more stringent at forensic laboratories. Since his conviction, some of the medical evidence against Norris has been called into question, especially the prevalence of spontaneous attacks of hypoglycemia in elderly and frail patients with co-morbidities.

  • 28.
    Jones, A Wayne
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Postmortem toxicology findings from medicolegal investigations of drug-related deaths among the rich and famous2017In: Toxicologie Analytique et Clinique, ISSN 2352-0078, Vol. 29, no 3, p. 298-308Article, review/survey (Refereed)
    Abstract [en]

    This article presents a review of medicolegal investigations of drug-related deaths among various Hollywood celebrities and popular music icons. The movie stars included: Marilyn Monroe, River Phoenix, John Belushi, Chris Penn, Heath Ledger and Philip Seymour Hoffman. The musicians are exemplified by Elvis Presley, Janis Joplin, Jimi Hendrix, Keith Moon, Sid Vicious, Kurt Cobain, Amy Winehouse, Michael Jackson, Whitney Houston and Prince. The tragic drug-related death of Anna Nicole Smith, a sex-symbol and Playboy model, is also included. The illicit drugs mainly responsible for the fatalities were heroin and/or cocaine or a mixture of the two narcotics. Some of the celebrity deaths were caused by inappropriate use of prescription medications, mostly combined influences of one or more benzodiazepine together with an opiate or opioid pain medication. Polypharmacy increases the risk of adverse drug events and this sometimes causes a sudden and unexpected death. As tolerance to the pharmacological effects of drugs develop, the amounts taken (the dose) are increased, which enhances the risk of a fatal drug-drug interaction. Ethanol was implicated in some of the celebrity deaths, which underscores the dangers of excessive drinking when taking centrally acting drugs. In the case of Amy Winehouse, a talented jazz singer, she died from acute alcohol poisoning, because ethanol was the only psychoactive drug identified in postmortem blood. © 2017 Société Française de Toxicologie Analytique

  • 29.
    Jones, A Wayne
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology.
    Scientometric evaluation of highly cited scientists in the field of forensic science and legal medicine2021In: International journal of legal medicine, ISSN 0937-9827, E-ISSN 1437-1596, Vol. 135, no 2, p. 701-707Article in journal (Refereed)
    Abstract [en]

    A publically available database of the most highly cited scientists in all disciplines was used to identify people that belonged to the subject category "forensic science and legal medicine." This bibliometric information was derived from Elseviers SCOPUS database containing eight million scientists with at least five articles as author or co-author. The top 100,000 most highly cited scientists were identified and ranked according to six citation metrics; total number of citations, H-index, H-index adjusted for co-authorship, citations to single-authored papers, citations to single or first author papers and, citations to single, first, or last-authored papers. The eight million entries in the SCOPUS database were sub-divided into 22 main subject categories and 176 sub-categories, one of which was legal and forensic medicine. The citation databases were provided as supplementary material in two articles published in PLoS Biology in 2019 and 2020. Among the top 100,000 most highly cited scientists, there were only 30 allocated to the legal and forensic medicine category, according to the 2019 PLoS Biology article. The updated database from 2020 also included the names of people within the top-cited 2% of their scientific discipline. This increased the number of forensic practitioners to 215 from a total of 10,158 individuals in this subject category. This article takes a closer look at these highly cited forensic scientists, the countries where they work, the particular research field in which they publish, and their composite citation scores with and without self-citations. The top ten most cited individuals in both databases (2019 and 2020) were the same and these should therefore be considered an elite group among all forensic practitioners.

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  • 30.
    Jones, A Wayne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Who are the most highly cited forensic scientists in the United States?2023In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 68, no 3, p. 723-730Article in journal (Other academic)
    Abstract [en]

    The most highly cited forensic practitioners in the United States were identified using a publicly available citation database that used six different citation metrics to calculate each persons composite citation score. The publication and citation data were gleaned from Elseviers SCOPUS database, which contained information about similar to 7 million scientist each of whom had at least five entries in the database. Each individual was categorized into 22 scientific fields and 176 subfields, one of which was legal and forensic medicine (LFM). The database contained citation records for 13,388 individuals having LFM as their primary research discipline and 282 of these (2%) were classified as being highly cited. Another 99 individuals in the database had LFM as their secondary discipline, making a total of 381 highly cited forensic practitioners from 35 different countries. The career-long publication records of each individual were compared using their composite citation scores. Of the 381 highly cited scientists, 93 (24%) had an address somewhere in the United States. The various branches of forensics they specialized in were anthropology, criminalistics, DNA/genetics, odontology, pathology, statistics/epidemiology, and toxicology. The two most highly cited scientists, according to their composite citation score, were both specialists in DNA/genetics. Bibliometric methods are widely used for evaluating research performance in academia and a similar approach might be useful in jurisprudence, such as when an expert witness is instructed to testify in court and explain the meaning of scientific evidence.

  • 31.
    Jones, A Wayne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Holmgren, Anita
    Swedish National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Swedish National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Post-mortem concentrations of drugs determined in femoral blood in single-drug fatalities compared with multi-drug poisoning deaths2016In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 267, p. 96-103Article in journal (Refereed)
    Abstract [en]

    Background: Reference concentrations of drugs in post-mortem femoral blood furnishes useful information when poisoning (intoxication) deaths are investigated. However, few publications compare the concentrations of drugs in single-drug fatalities with multi-drug intoxications. This article attempts to fill this gap in knowledge. Methods: We searched a national forensic toxicology database (TOXBASE) and found N = 13,963 deaths attributed by pathologists to intoxication by drugs (poisoning). The manner of death, whether accidental, suicidal or undetermined intent, was also available. To compare drug concentrations in living and deceased persons, we used information from people arrested for driving under the influence of drugs (DUID). Results: The percentage of drug intoxication deaths classified as undetermined intent decreased and accidental overdose deaths increased during the study period. In 2010 manner of death was considered accidental, suicidal or undetermined, in 41%, 30% and 28% of victims, respectively. Most of the deceased had taken multiple drugs (mean three drugs/case) and four or more drugs were identified in 35% of deaths. In single-drug fatalities ethanol (1585), morphine (114), citalopram (28), propoxyphene (51), flunitrazepam (70), propiomazine (46), tramadol (20) and zopiclone (15) were most prevalent. Alprazolam and diazepam were common findings in multi-drug deaths, although these benzodiazepines were rarely encountered in mono-drug intoxication deaths. Median blood concentrations were appreciably higher (2-10 fold) in single-drug fatalities compared with multi-drug deaths. The blood concentrations in DUID suspects were mostly lower than in the multi-drug poisoning deaths. Conclusion: This compilation of femoral blood concentrations of drugs in poisoning deaths provides a useful reference material, because we have distinguished between mono-drug intoxication deaths and poisoning with multiple-drugs. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 32.
    Jones, A Wayne
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Tilson, Christopher
    Georgia Bur Invest, GA USA.
    Comments: Distribution ratios of ethanol and water between whole blood, plasma, serum, and erythrocytes: Recommendations for interpreting clinical laboratory results in a legal context2023In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 68, no 1, p. 9-21Article in journal (Other academic)
    Abstract [en]

    This article reviews the scientific literature dealing with the distribution of ethanol and water between whole blood (WB), plasma, serum, and erythrocytes (red-blood cells). Knowledge of the ethanol distribution ratio is important when analytical results derived from hospital clinical laboratories are interpreted in a forensic context, such as during the prosecution of traffic offenders. Statutory blood-alcohol concentration (BAC) limits for driving are defined as the concentration of ethanol in WB and not in plasma, serum or red-blood cells. These bio-fluids differ in their water content and thereby the concentrations of ethanol. Plasma and serum contain similar to 90%-92% w/w water, WB similar to 78%-80% w/w and erythrocytes similar to 64%-66% w/w. The mean plasma/WB and serum/WB distribution ratios of ethanol are therefore expected to be similar to 1.15:1 (91/79 = 1.15), which is in good agreement with values determined empirically. However, in individual cases, the actual distribution ratio will depend on the persons age, gender, and biochemical and hematological properties of the blood specimen, such as its hematocrit. For legal purposes, we recommend that the concentration of ethanol in plasma or serum determined at hospital laboratories is divided by a factor of 1.2, which would provide a conservative estimate of the co-existing BAC and the chance of overestimating the true value is only 1 in 2000 (0.05%).

  • 33.
    Jones, Alan Wayne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    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 contrasted2024In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029Article in journal (Refereed)
    Abstract [en]

    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.

  • 34.
    Jones, Alan Wayne
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Holmgren, Anita
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    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 autopsy2015In: International journal on drug policy, ISSN 0955-3959, E-ISSN 1873-4758, Vol. 26, no 8, p. 790-793Article in journal (Refereed)
    Abstract [en]

    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.

  • 35.
    Jönsson, Anna K
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pharmacology.
    Soderberg, Carl
    Karolinska Institute, Sweden .
    Arne Espnes, Ketil
    St Olavs University Hospital, Norway .
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Eriksson, Anders
    Umeå University, Sweden .
    Reis, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Druid, Henrik
    Karolinska Institute, Sweden .
    Sedative and hypnotic drugs-Fatal and non-fatal reference blood concentrations2014In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 236, p. 138-145Article in journal (Refereed)
    Abstract [en]

    In postmortem investigations of fatal intoxications it is often challenging to determine which drug/s caused the death. To improve the interpretation of postmortem blood concentrations of sedative and hypnotic drugs and/or clonazepam, all medico-legal autopsies in Sweden - where these drugs had been detected in femoral vein blood during 1992-2006 - were identified in the databases of the National Board of Forensic Medicine. For each drug, concentrations in postmortem control cases - where the cause of death was not intoxication and where incapacitation by drugs could be excluded - were compiled as well as the levels found in living subjects; drugged driving cases and therapeutic drug monitoring cases. Subsequently, fatal intoxications were assessed with regards to the primary substances contributing to death, and blood levels were compiled for single and multiple drug intoxications. The postmortem femoral blood levels are reported for 16 sedative and hypnotic drugs, based on findings in 3560 autopsy cases. The cases were classified as single substance intoxications (N = 498), multiple substance intoxications (N = 1555) and postmortem controls (N = 1507). Each autopsy case could be represented more than once in the group of multiple intoxications and among the postmortem controls if more than one of the included substances were detected. The concentration ranges for all groups are provided. Overlap in concentrations between fatal intoxications and reference groups was seen for most substances. However, the concentrations found in single and multiple intoxications were significantly higher than concentrations found in postmortem controls for all substances except alprazolam and triazolam. Concentrations observed among drugged drivers were similar to the concentrations observed among the therapeutic drug monitoring cases. Flunitrazepam was the substance with the highest number of single intoxications, when related to sales. In summary, this study provides reference drug concentrations primarily to be used for improving interpretation of postmortem drug levels in obscure cases, but which also may assist in drug safety work and in pharmacovigilance efforts.

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  • 36.
    Kadane, Joseph B.
    et al.
    Carnegie Mellon Univ, PA 15213 USA.
    Nordgaard, Anders
    Linköping University, Department of Computer and Information Science, The Division of Statistics and Machine Learning. Linköping University, Faculty of Arts and Sciences.
    Using Bayes factors to limit forensic testimony to forensics: composite hypotheses2024In: Australian journal of forensic sciences, ISSN 0045-0618Article in journal (Refereed)
    Abstract [en]

    In most western legal systems, only the fact-finder (judge or jury) is entrusted to make the ultimate decision in a criminal case. A forensic expert can help the fact-finder by opining on the weight of the forensic evidence given the hypotheses relevant to the case, but is not qualified to give an opinion about the ultimate question(s). When the question is reduced to two simple hypotheses, a Bayes Factor can express the expert's opinion about the extent to which the forensic evidence favours each hypothesis. This paper addresses the situation in which one or both of the hypotheses are composite, that is, embrace more than one possibility. It offers an interval of Bayes Factors, and shows that the proposed interval includes those values, and only those values, of the Bayes Factor supported by possible beliefs of the fact-finder. Shoe prints, tool marks and DNA are discussed in this light if the hypotheses used in the Bayes Factor are composite.

  • 37.
    Kokshoorn, Bas
    et al.
    Division Biological Traces, Netherlands Forensic Institute, The Hague, the Netherlands.
    Aarts, Lambertus H.J.
    Division Biological Traces, Netherlands Forensic Institute, The Hague, the Netherlands.
    Ansell, Ricky
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering. Swedish National Forensic Centre, Sweden.
    Connolly, Edward
    Forensic Science Ireland, Garda HQ, Phoenix Park, Ireland.
    Drotz, Weine
    Swedish National Forensic Centre, Linköping, Sweden.
    Kloosterman, Ate D.
    Division Biological Traces, Netherlands Forensic Institute, The Hague, the Netherlands.
    McKenna, Louise G.
    Forensic Science Ireland, Garda HQ, Ireland.
    Szkuta, Bianca
    Office of the Chief Forensic Scientist, Victoria Police Forensic Services Department, Australia; School of Life and Environmental Sciences, Deakin University, Australia.
    van Oorschot, Roland A.H.
    Office of the Chief Forensic Scientist, Victoria Police Forensic Services Department, Australia; School of Molecular Sciences, La Trobe University, Australia.
    Sharing data on DNA transfer, persistence, prevalence and recovery: Arguments for harmonization and standardization2018In: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 37, p. 260-269Article in journal (Refereed)
    Abstract [en]

    Sharing data between forensic scientists on DNA transfer, persistence, prevalence and recovery (TPPR) is crucial to advance the understanding of these issues in the criminal justice community. We present the results of a collaborative exercise on reporting forensic genetics findings given activity level propositions. This exercise outlined differences in the methodology that was applied by the participating laboratories, as well as limitations to the use of published data on DNA TPPR. We demonstrate how publication of experimental results in scientific journals can be further improved to allow for an adequate use of these data. Steps that can be taken to share and use these data for research and casework purposes are outlined, and the prospects for future sharing of data through publicly accessible databases are discussed. This paper also explores potential avenues to proceed with implementation and is intended to fuel the discussion on sharing data pertaining to DNA TPPR issues. It is further suggested that international standardization and harmonization on these topics will benefit the forensic DNA community as it has been achieved in the past with the harmonization of STR typing systems.

  • 38.
    Kronstrand, Christoffer
    et al.
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Nilsson, Gunnel
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Cherma, Maria D.
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Evaluating the hip-flask defence in subjects with alcohol on board: An experimental study2019In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 294, p. 189-195Article in journal (Refereed)
    Abstract [en]

    Driving under the influence of alcohol is a major problem for traffic-safety and a popular defence argument is alleged consumption after driving, commonly referred to as the hip-flask defence. Forensic toxicologists are often called as expert witnesses in drinking and driving cases where the suspect has claimed the hip-flask defence, to assess the credibility of the explanation. Several approaches to help the expert have been introduced but the scientific data used to support or challenge this is solely based on data from controlled single doses of ethanol administered during a short time and in abstinent subjects. In reality, we believe that even in drinking after driving cases, the subject many times has alcohol on board at time of the hip-flask drink. This questions the applicability of the data used as basis to investigate the hip-flask defence. To fill this knowledge gap, we aimed to investigate how blood and urine ethanol kinetics vary after an initial drinking session of beer and then a subsequent hip-flask drink of three different doses of whiskey. Fifteen subjects participated in the study and each provided 10 urine samples and 17 blood samples over 7 h. The initial drink was 0.51 g ethanol/kg and the second was either 0.25, 0.51, or 0.85 g/kg. Our data suggested that the difference between the ethanol concentrations in two consecutive urine samples is a more sensitive parameter than the ratio between urine and blood alcohol to detect a recent intake when ethanol from previous intakes are already present in the body. Twelve subjects presented results that fully supported a recent intake using the criteria developed from a single intake of ethanol. Three subjects showed unexpected results that did not fully support a recent intake. We conclude that data from one blood sample and two urine samples provide good evidence for investigating the hip-flask defence even if alcohol was on board at the time of the hip-flask drink. (C) 2018 Elsevier B.V. All rights reserved.

  • 39.
    Kronstrand, Robert
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Forsman, Malin
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Roman, Markus
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Quantitative analysis of drugs in hair by UHPLC high resolution mass spectrometry2018In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 283Article in journal (Refereed)
    Abstract [en]

    Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are few recommendations regarding the parameters and their criteria to identify a compound. In this study we present a method for the identification and quantification of a range of drugs and discuss the parameters used to identify a compound with high resolution mass spectrometry. Drugs were extracted from hair by incubation in a buffer: solvent mixture at 37 degrees C during 18 h. Analysis was performed on a chromatographic system comprised of an Agilent 6550 QTOF coupled to a 1290 Infinity UHPLC system. High resolution accurate mass data were acquired in the All Ions mode and exported into Mass Hunter Quantitative software for quantitation and identification using qualifier fragment ions. Validation included selectivity, matrix effects, calibration range, within day and between day precision and accuracy. The analytes were 7-amino-flunitrazepam, 7-amino-clonazepam, 7-amino-nitrazepam, acetylmorphine, alimemazine, alprazolam, amphetamine, benzoylecgonine, buprenorphine, diazepam, ethylmorphine, fentanyl, hydroxyzine, ketobemidone, codeine, cocaine, MDMA, methadone, methamphetamine, morphine, oxycodone, promethazine, propiomazine, propoxyphene, tramadol, zaleplone, zolpidem, and zopiclone. As proof of concept, hair from 29 authentic post mortem cases were analysed. The calibration range was established between 0.05 ng/mg to 5.0 ng/mg for all analytes except fentanyl (0.02-2.0), buprenorphine (0.04-2.0), and ketobemidone (0.05-4.0) as well as for alimemazine, amphetamine, cocaine, methadone, and promethazine (0.10-5.0). For all analytes, the accuracy of the fortified pooled hair matrix was 84-108% at the low level and 89-106% at the high level. The within series precisions were between 1.4 and 6.7% and the between series precisions were between 1.4 and 10.1%. From the 29 autopsy cases, 121 positive findings were encountered from 23 of the analytes in concentrations similar to those previously published. We conclude that the developed method proved precise and accurate and that it had sufficient performance for the purpose of detecting regular use of drugs or treatment with prescription drugs. To identify a compound we recommend the use of ion ratios as a complement to instrument software "matching scores". (c) 2018 Elsevier B.V. All rights reserved.

  • 40.
    Levin, Sara
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Department of Forensic Psychiatry.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bendtsen, Preben
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Bülow, Per
    Region Östergötland, Local Health Care Services in West Östergötland, Department of Forensic Psychiatry. Department of Psychiatry, Ryhov County Hospital, Jönköping, Sweden; Department of Behavioural Science and Social Work, School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Adherence to planned risk management interventions in Swedish forensic care: What is said and done according to patient records2019In: International Journal of Law and Psychiatry, ISSN 0160-2527, E-ISSN 1873-6386, Vol. 64, p. 71-82Article in journal (Refereed)
    Abstract [en]

    Both structured and unstructured clinical risk assessments within forensic care aim to prevent violence by informing risk management, but research about their preventive role is inconclusive. The aim of this study was to investigate risk management interventions that were planned and realized during forensic care by analysing patient records. Records from a forensic clinic in Sweden, covering 14 patients and 526 months, were reviewed. Eight main types of risk management interventions were evaluated by content analysis: monitoring, supervision, assessment, treatment, victim protection, acute coercion, security level and police interventions. Most planned risk management interventions were realized, both in structured and clinical risk assessments. However, most realized interventions were not planned, making them more open to subjective decisions. Analysing risk management interventions actually planned and realized in clinical settings can reveal the preventive role of structured risk assessments and how different interventions mediate violence risk.

  • 41.
    Lin, Zijie
    et al.
    Fudan Univ, Peoples R China.
    Wang, Hao
    Fudan Univ, Peoples R China.
    Jones, A Wayne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Wang, Fanglin
    Minist Publ Secur, Peoples R China.
    Zhang, Yunfeng
    Minist Publ Secur, Peoples R China.
    Rao, Yulan
    Fudan Univ, Peoples R China.
    Evaluation and review of ways to differentiate sources of ethanol in postmortem blood2020In: International journal of legal medicine, ISSN 0937-9827, E-ISSN 1437-1596, Vol. 134, p. 2081-2093Article, review/survey (Refereed)
    Abstract [en]

    Accurate determination of a persons blood alcohol concentration (BAC) is an important task in forensic toxicology laboratories because of the existence of statutory limits for driving a motor vehicle and workplace alcohol testing regulations. However, making a correct interpretation of the BAC determined in postmortem (PM) specimens is complicated, owing to the possibility that ethanol was produced in the body after death by the action of various micro-organisms (e.g., Candida species) and fermentation processes. This article reviews various ways to establish the source of ethanol in PM blood, including collection and analysis of alternative specimens (e.g., bile, vitreous humor (VH), and bladder urine), the identification of non-oxidative metabolites of ethanol, ethyl glucuronide (EtG) and ethyl sulfate (EtS), the urinary metabolites of serotonin (5-HTOL/5-HIAA), and identification ofn-propanol andn-butanol in blood, which are known putrefaction products. Practical utility of the various biomarkers including specificity and stability is discussed.

  • 42. Order onlineBuy this publication >>
    Lood, Yvonne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Testosterone Use and Abuse: Methodological Aspects in Forensic Toxicology and Clinical Diagnostics2021Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Abuse of anabolic androgenic steroids (AAS) is widespread in society and is today a major public health problem, associated with mental and somatic adverse effects and risk behavior, such as use of other illicit drugs and criminality. Testosterone, the most important endogenous male androgen, is therapeutically used in replacement therapy but is also extensively used as a doping agent. Traditionally, testosterone abuse is detected in urine in forensic cases and in serum in clinical diagnosis and monitoring, and free bioavailable serum testosterone is calculated by formulas. Salivary testosterone is however an attractive biomarker, as testosterone in saliva is supposed to reflect free testosterone in serum. 

    The aim of this thesis was to investigate the abuse of AAS from a forensic perspective, particularly focusing on testosterone and methodological problems and potential alternative matrices for measurements of testosterone in forensic and clinical assessments. 

    In the first study the toxicological findings in individuals suspected of doping offences, registered in the Swedish national forensic toxicology database were investigated (paper I). In paper II, testosterone levels in serum, saliva, and urine in clinical patients during replacement therapy with testosterone undecanoate (Nebido®) were studied. Further, the sensitivity of the current procedure for detection of testosterone abuse was investigated by method comparison using isotope ratio measurement (paper III) and a quantitative LC-MS/MS method for testosterone in serum and saliva was developed and presented (paper IV). 

    It was found that testosterone was most frequently detected in the forensic cases and co-abuse of narcotics was common among AAS abusers. Methodological problems in detection of testosterone abuse using the present procedures was identified, indicating a need for new analytical strategies. A sensitive and highly specific LC-MS/MS method was developed for determination of testosterone in serum and saliva, which was shown suitable for analysis of forensic and clinical samples. Salivary testosterone was shown to correlate well with free serum testosterone in both male and female, and a sensitive marker in testosterone therapy, especially in females. In conclusion, it was found that saliva might have a potential as an alternative matrix for detection of illicit administration of testosterone and for diagnosis and monitoring of androgenic status. 

    List of papers
    1. Anabolic androgenic steroids in police cases in Sweden 1999-2009
    Open this publication in new window or tab >>Anabolic androgenic steroids in police cases in Sweden 1999-2009
    2012 (English)In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 219, no 1-3, p. 199-204Article in journal (Refereed) Published
    Abstract [en]

    Anabolic Androgenic Steroids (AAS) are considered drugs of abuse and are controlled substances in Sweden since 1999. Traditionally AAS have been used by elite athletes to enhance performance, but in recent years it has become an increasing problem outside elite sport among athletes, bodybuilders and criminals. Use of AAS is associated with psychiatric side effects such as aggression, depression and violent behavior. Supraphysiological doses and long term use can cause serious physical harm such as cardiovascular toxicity and even premature death. We investigated and evaluated the drug analytical findings in forensic cases from suspected perpetrators in cases from the police where a screening for AAS was requested to get information about the prevalence of AAS use and the occurrence of poly-drug abuse. The study was based on samples submitted from the police authorities to the Department of Forensic Toxicology in Sweden during the period 1999-2009. Urines were analyzed by methods based on GC-MS and LC-MS-MS. We also analyzed the prevalence of AAS use at the prison and probation services. A total number of 12,141 urine samples (6362 police cases and 5779 inmates) were analyzed and 33.5% of the cases from the police and 11.5% of the inmates were tested positive for AAS. The users of AAS were mainly in 99.2% men with a mean age of 26.2 +/- 6.2 years whereas the women were 29.5 +/- 6.5 years old. The most frequently used AAS was nandrolone followed by testosterone and methandienone. Other illicit and licit drugs were detected in 60% of the cases from the police, strongly indicating a frequent poly-drug abuse among users of AAS.

    Place, publisher, year, edition, pages
    Elsevier, 2012
    Keywords
    Anabolic androgenic steroids, Forensic toxicology, Drugs of abuse, Testosterone
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-78810 (URN)10.1016/j.forsciint.2012.01.004 (DOI)000304626800034 ()
    Available from: 2012-06-21 Created: 2012-06-21 Last updated: 2021-02-04
    2. Relationship between testosterone in serum, saliva and urine during treatment with intramuscular testosterone undecanoate in gender dysphoria and male hypogonadism
    Open this publication in new window or tab >>Relationship between testosterone in serum, saliva and urine during treatment with intramuscular testosterone undecanoate in gender dysphoria and male hypogonadism
    Show others...
    2018 (English)In: Andrology, ISSN 2047-2919, E-ISSN 2047-2927, Vol. 6, no 1, p. 86-93Article in journal (Refereed) Published
    Abstract [en]

    Long-term testosterone replacement therapy is mainly monitored by trough levels of serum testosterone (S-T), while urinary testosterone (U-T) is used by forensic toxicology to evaluate testosterone doping. Testosterone in saliva (Sal-T) may provide additional information and simplify the sample collection. We aimed to investigate the relationships between testosterone measured in saliva, serum and urine during standard treatment with 1,000mg testosterone undecanoate (TU) every 12th week during 1year. This was an observational study. Males with primary and secondary hypogonadism (HG; n=23), subjects with gender dysphoria (GD FtM; n=15) and a healthy control group of men (n=32) were investigated. Sal-T, S-T and U-T were measured before and after TU injections. Sal-T was determined with Salimetrics((R)) enzyme immunoassay, S-T with Roche Elecsys((R)) testosterone II assay and U-T by gas chromatography-mass spectrometry. Sal-T correlated significantly with S-T and calculated free testosterone in both controls and patients (HG men and GD FtM), while Sal-T to U-T showed weaker correlations. Trough values of Sal-T after 12months were significantly higher in the GD FtM group (0.77 +/- 0.35nmol/L) compared to HG men (0.53 +/- 0.22nmol/L) and controls (0.46 +/- 0.15nmol/L), while no differences between S-T and U-T trough values were found. Markedly elevated concentrations of salivary testosterone, 7-14days after injection, were observed, especially in the GD FtM group. This study demonstrates that Sal-T might be a useful clinical tool to monitor long-term testosterone replacement therapy and might give additional information in forensic cases.

    Place, publisher, year, edition, pages
    WILEY, 2018
    Keywords
    doping; gender dysphoria; hypogonadism; saliva; testosterone
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:liu:diva-144253 (URN)10.1111/andr.12435 (DOI)000418797400012 ()29145707 (PubMedID)
    Note

    Funding Agencies|Medical Research Council of Southeast Sweden; Linkoping University, Sweden

    Available from: 2018-01-12 Created: 2018-01-12 Last updated: 2021-12-28
    3. False negative results in testosterone doping in forensic cases: Sensitivity of the urinary detection criteria T/E and T/LH
    Open this publication in new window or tab >>False negative results in testosterone doping in forensic cases: Sensitivity of the urinary detection criteria T/E and T/LH
    Show others...
    2021 (English)In: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. n/a, no n/aArticle in journal (Refereed) Published
    Abstract [en]

    At the Swedish national forensic toxicology laboratory, a measured testosterone/epitestosterone (T/E) ratio?≥?12 together with testosterone/luteinizing hormone (T/LH) in urine?>?400?nmol/IU is considered as a proof of exogenous testosterone administration. However, according to the rules of the World Anti-Doping Agency (WADA), samples with T/E ratio?>?4 are considered suspicious and shall be further analysed by gas chromatography?combustion?isotope ratio mass spectrometry (GC-C-IRMS) to confirm the origin of testosterone and its metabolites. The aim of this study was to investigate the possibility of false negative results and to estimate the frequency of negative results using the current criteria for detection of abuse of testosterone in forensic investigations. Urine and serum samples were collected by the police at suspected infringement of the doping law in Sweden. Fifty-eight male subjects were included in the study. Urinary testosterone was determined by gas chromatography?mass spectrometry (GC?MS), serum testosterone and LH?by immunoassay. The origin of testosterone and its metabolites was confirmed by means of GC-C-IRMS. Twenty-six of the 57 analysed subjects tested positive for exogenous testosterone using the criteria T/E?≥?12 combined with T/LH?>?400?nmol/IU. The IRMS analyses confirmed 47 positives; thus, 21 were considered false negatives. Negative predictive value was 32% (95% confidence interval [CI]: 16%?50%) and sensitivity 55%. No false positive subjects were found. The number of false negative cases using the current criteria for the detection of testosterone abuse and hence the low sensitivity indicates a need to discuss introduction of new strategies in forensic doping investigations.

    Place, publisher, year, edition, pages
    John Wiley & Sons, Ltd, 2021
    Keywords
    doping, GC-C-IRMS, LH, T/E, testosterone
    National Category
    Forensic Science
    Identifiers
    urn:nbn:se:liu:diva-178310 (URN)10.1002/dta.3125 (DOI)000674047600001 ()
    Conference
    2021/08/17
    Note

    Funding agencies: Strategic Research Area in Forensic Science (2019), Sweden

    Available from: 2021-08-17 Created: 2021-08-17 Last updated: 2022-06-17Bibliographically approved
    4. Determination of testosterone in serum and saliva by liquid chromatography-tandem mass spectrometry: An accurate and sensitive method applied on clinical and forensic samples
    Open this publication in new window or tab >>Determination of testosterone in serum and saliva by liquid chromatography-tandem mass spectrometry: An accurate and sensitive method applied on clinical and forensic samples
    Show others...
    2021 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 195, article id 113823Article in journal (Refereed) Published
    Abstract [en]

    A highly sensitive and accurate electrospray liquid chromatography tandem-mass spectrometry (ESI-LC–MS/MS) method for determination of testosterone in human serum and saliva was developed and validated. Accurate quantification of testosterone in human matrices is essential in diagnosis and management of androgen status in men, women and children, and in forensic investigations of suspected abuse of anabolic androgenic steroids. Chromatography was performed on an HSS-T3 C18 column with a total run-time of 5.5 min. The tandem mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Serum and saliva samples of 200 μL, were prepared by solid-phase extraction using a 96-well plate following precipitation with 200 μL methanol. 13C labeled testosterone was used as internal standard for quantification. The standard curve was linear within the range of 4−1000 pg/mL and the limit of quantification of both serum and salivary testosterone was 4 pg/mL. Accuracy were 99–101 % and 93–95 % with between-run imprecision in serum and saliva, respectively, and inter- and intra-assay coefficients of variation were less than 9.2 %. The method proved to be applicable for determination of testosterone over a wide range of concentrations in serum and saliva samples from clinical patients with various androgen disorders, healthy male and female adults as well as from forensic cases.

    Place, publisher, year, edition, pages
    Elsevier, 2021
    Keywords
    Testosterone, Serum, Saliva, LC–MS/MS
    National Category
    Analytical Chemistry
    Identifiers
    urn:nbn:se:liu:diva-173145 (URN)10.1016/j.jpba.2020.113823 (DOI)000610841900007 ()113823 (Local ID)113823 (Archive number)113823 (OAI)
    Note

    Funding:Strategic Area in Forensic Science; Forskningsradet i Sydostra Sverige (FORSS) [713391]

    Available from: 2021-02-04 Created: 2021-02-04 Last updated: 2022-05-23Bibliographically approved
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  • 43.
    Lood, Yvonne
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Aardal, Elisabeth
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Gustavsson, Sara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Prasolov, Ilya
    Swedish Doping Control Laboratory, Karolinska University Hospital, Stockholm, Sweden.
    Josefsson, Martin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Drug Unit Department, National Forensic Centre, Linköping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    False negative results in testosterone doping in forensic cases: Sensitivity of the urinary detection criteria T/E and T/LH2021In: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. n/a, no n/aArticle in journal (Refereed)
    Abstract [en]

    At the Swedish national forensic toxicology laboratory, a measured testosterone/epitestosterone (T/E) ratio?≥?12 together with testosterone/luteinizing hormone (T/LH) in urine?>?400?nmol/IU is considered as a proof of exogenous testosterone administration. However, according to the rules of the World Anti-Doping Agency (WADA), samples with T/E ratio?>?4 are considered suspicious and shall be further analysed by gas chromatography?combustion?isotope ratio mass spectrometry (GC-C-IRMS) to confirm the origin of testosterone and its metabolites. The aim of this study was to investigate the possibility of false negative results and to estimate the frequency of negative results using the current criteria for detection of abuse of testosterone in forensic investigations. Urine and serum samples were collected by the police at suspected infringement of the doping law in Sweden. Fifty-eight male subjects were included in the study. Urinary testosterone was determined by gas chromatography?mass spectrometry (GC?MS), serum testosterone and LH?by immunoassay. The origin of testosterone and its metabolites was confirmed by means of GC-C-IRMS. Twenty-six of the 57 analysed subjects tested positive for exogenous testosterone using the criteria T/E?≥?12 combined with T/LH?>?400?nmol/IU. The IRMS analyses confirmed 47 positives; thus, 21 were considered false negatives. Negative predictive value was 32% (95% confidence interval [CI]: 16%?50%) and sensitivity 55%. No false positive subjects were found. The number of false negative cases using the current criteria for the detection of testosterone abuse and hence the low sensitivity indicates a need to discuss introduction of new strategies in forensic doping investigations.

  • 44.
    Maskell, Peter D.
    et al.
    Univ Glasgow, Scotland.
    Jones, A Wayne
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Heymsfield, Steven B.
    Louisiana State Univ, LA 70808 USA.
    Shapses, Sue
    Rutgers State Univ, NJ USA.
    Johnston, Atholl
    Queen Mary Univ London, England; St Georges Univ London, England.
    Total body water is the preferred method to use in forensic blood-alcohol calculations rather than ethanols volume of distribution2020In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 316, article id 110532Article in journal (Refereed)
    Abstract [en]

    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. 80 mg/100 mL, 0.08 g/100 mL or 0.80 g/L). For this purpose, most forensic scientists utilize the Widmark equation, or some modification thereof, to calculate a persons 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 persons 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 80 kg/m(2). 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 35 kg/m(2) and that the Watson et al. equation works for those with more extreme BMI; females (17-80 kg/m(2)) and males (17-67 kg/m(2)). (C) 2020 Elsevier B.V. All rights reserved.

  • 45.
    Maskell, Peter D.
    et al.
    Abertay Univ, Scotland.
    Jones, A Wayne
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Savage, Anne
    Abertay Univ, Scotland.
    Scott-Ham, Michael
    Principal Forens Serv, England.
    Evidence based survey of the distribution volume of ethanol: Comparison of empirically determined values with anthropometric measures2019In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 294, p. 124-131Article in journal (Refereed)
    Abstract [en]

    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 (V-d) of ethanol, which is commonly referred to as the rho-factor. Although a persons V-d 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 persons total body water (TBW) and hence V-d of ethanol. To date, there are not any studies that compare V-d derived from anthropometric data with robust values measured empirically. From the literature we compiled information about the V-d of ethanol from drinking studies with 173 Caucasian males and 63 Caucasian females from Western Europe. These empirically derived values of V-d 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 0.00 L/kg) and 95% range +/- 0.13 L/kg. The equation derived by Forrest, which took into consideration a persons body mass index (BMI), gave the best estimates of V-d for females; mean bias -0.01 L/kg and range +/- 0.15 L/kg. (C) 2018 Elsevier B.V. All rights reserved.

  • 46.
    Moche, Hajdi
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Karlsson, Hulda
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Västfjäll, Daniel
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Decis Res, OR USA.
    Victim identifiability, number of victims, and unit asking in charitable giving2024In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 3, article id e0300863Article in journal (Refereed)
    Abstract [en]

    This study examines the identifiable victim effect (being more willing to help an identified victim than an unidentified), the singularity effect (i.e., being more willing to help a single identified victim than a group of identified victims), and unit asking (first asking donors for their willingness to donate for one unit and then asking for donations for multiple units) in charitable giving. In five studies (N = 7996), we vary the level of identifiability, singularity, and group size. We find that unit asking is making people more sensitive to the number of people in need. Further, while the level of identifiability influences affective reactions, this effect does not extend to donations and, thus, is not affected by unit asking. We do, however, find an "emotion asking effect" where asking donors to rate their affect before donating increase donation levels (compared to donors asked to rate affect after). Emotion asking was attenuated when combined with unit asking.

  • 47.
    Nilsson, Gunnel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Validation of an LC-MS/MS method for the determination of zopiclone, N-desmethylzopiclone and 2-amino-5-chloropyridine in whole blood and its application to estimate the original zopiclone concentration in stored specimens2015In: International journal of legal medicine, ISSN 0937-9827, E-ISSN 1437-1596, Vol. 129, no 2, p. 269-277Article in journal (Refereed)
    Abstract [en]

    2-amino-5-chloropyridine (ACP) is a degradation product of zopiclone (ZOP) and may be formed when blood specimens are stored. ZOP instability in blood makes interpretation of concentrations difficult especially in cases of prolonged sample storage. This study investigated how ACP could be used to estimate the original concentration of ZOP in authentic samples. For that purpose, an analytical LC-MS/MS method for the quantitation of ACP, ZOP and the metabolite Ndesmethylzopiclone (NDZOP) in blood was validated. The method was then applied to investigate ACP formation, ZOP and NDZOP degradation in stored ZOP post-dosed authentic whole blood and two mathematical models were used to calculate the original concentration of ZOP. During storage, ACP was formed in amounts equimolar to the ZOP and NDZOP degradation. Results from samples in which ACP had been formed were used to test two models to estimate the original ZOP concentration. The correlation tests of the models showed strong correlations to the original ZOP concentration (r=0.960 and r=0.955) with p<0.01. This study showed that the equimolar degradation of ZOP and NDZOP to ACP could be used to estimate the original concentration of the unstable ZOP.

  • 48.
    Olsson, Martin O.
    et al.
    Psychiatry, Department of Clinical Sciences, Lund, Faculty of Medicine, Lund University, Sweden.
    Öjehagen, Agneta
    Psychiatry, Department of Clinical Sciences, Lund, Faculty of Medicine, Lund University, Sweden.
    Brådvik, Louise
    Psychiatry, Department of Clinical Sciences, Lund, Faculty of Medicine, Lund University, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, Swedish National Board of Forensic Medicine, Linköping, Sweden.
    Håkansson, Anders
    Psychiatry, Department of Clinical Sciences, Lund, Faculty of Medicine, Lund University, Sweden.
    High Rates of Tramadol Use among Treatment-Seeking Adolescents in Malmö, Sweden: A Study of Hair Analysis of Nonmedical Prescription Opioid Use2017In: Journal of addiction, ISSN 2090-7850, Vol. 2017, article id 6716929Article in journal (Refereed)
    Abstract [en]

    Nonmedical prescription opioid use (NMPOU) is a growing problem and tramadol has been suggested as an emerging problem in young treatment-seeking individuals. The aim of the present study was to investigate, through hair analysis, NMPOU in this group and, specifically, tramadol use.

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  • 49.
    Oshaug, Katja
    et al.
    Oslo Univ Hosp, Norway.
    Kronstrand, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Kugelberg, Fredrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Kristoffersen, Lena
    Oslo Univ Hosp, Norway.
    Morland, Jorg
    Norwegian Inst Publ Hlth, Norway.
    Hoiseth, Gudrun
    Oslo Univ Hosp, Norway; Univ Oslo, Norway; Diakonhjemmet Hosp, Norway.
    Frequency of postmortem ethanol formation in blood, urine and vitreous humor - Improving diagnostic accuracy with the use of ethylsulphate and putrefactive alcohols2022In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 331, article id 111152Article in journal (Refereed)
    Abstract [en]

    Purpose: This study aimed to compare the frequency of postmortem ethanol formation in blood, urine and vitreous humor according to negative ethylsulphate (EtS) in blood or positive putrefactive alcohols (PAs) in either medium. Furthermore, it aimed to evaluate the interpretational value of calculated ethanol ratios in relation to EtS and PA results. Methods: Blood ethanol positive forensic cases were included; one dataset consisting of 2504 cases with EtS analysed in blood and another dataset with 8001 cases where PAs were analysed. Results: PAs were found in 24.4% of cases. EtS was negative in 15.3%, 9.4% and 7.4% of cases that were positive for ethanol in blood, urine and vitreous humor, respectively. In EtS negative cases, the concentrations of ethanol in blood, urine and vitreous humor were lower than 0.20 g/kg in 51.3%, 67.4% and 77.8%, respectively. It was 1.0 g/kg or higher in blood in 4.2% of cases. More EtS negative and PA positive cases were seen in central compared to peripheral blood. Ethanol ratios between urine or vitreous humor and blood were significantly lower in both EtS negative and PA positive cases, but large variations were observed. Conclusion: EtS and PA analysis improve the diagnostic accuracy of ethanol in postmortem cases. Postmortem ethanol formation in vitreous humor and urine were both more frequent than expected and we recommend the analysis of ethanol primarily in peripheral blood if available. (c) 2021 The Author(s). Published by Elsevier B.V. CC_BY_4.0

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  • 50.
    Simona Chisalita, Ioana
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Chong, Lee Ti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Wajda, Maciej
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Adolfsson, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Woisetschläger, Mischa
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Association of Insulin-like Growth Factor-1, Bone Mass and Inflammation to Low-energy Distal Radius Fractures and Fracture Healing in Elderly Women Attending Emergency Care2017In: ORTHOPAEDIC SURGERY, ISSN 1757-7853, Vol. 9, no 4, p. 380-385Article in journal (Refereed)
    Abstract [en]

    Objective

    Elderly patients suffer fractures through low-energy mechanisms. The distal radius is the most frequent fracture localization. Insulin-like growth factor-1 (IGF1) plays an important role in the maintenance of bone mass and its levels decline with advancing age and in states of malnutrition. Our aim was to investigate the association of IGF1 levels, bone mass, nutritional status, and inflammation to low-energy distal radius fractures and also study if fracture healing is influenced by IGF1, nutritional status, and inflammation.

    Methods

    Postmenopausal women, 55 years or older, with low-energy distal radius fractures occurring due to falling on slippery ground, indoors or outdoors, were recruited in the emergency department (ED) and followed 1 and 5 weeks after the initial trauma with biomarkers for nutritional status and inflammation. Fractures were diagnosed according to standard procedure by physical examination and X-ray. All patients were conservatively treated with plaster casts in the ED. Patients who needed interventions were excluded from our study. Fracture healing was evaluated from radiographs. Fracture healing assessment was made with a five-point scale where the radiological assessment included callus formation, fracture line, and stage of union. Blood samples were taken within 24 h after fracture and analyzed in the routine laboratory. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA).

    Results

    Thirty-eight Caucasian women, aged 70.5 8.9 years (mean +/- SD) old, were recruited. Nutritional status, as evaluated by albumin (40.3 +/- 3.1 g/L), IGF1 (125.3 +/- 39.9 g/L), body mass index (26.9 +/- 3.6 kg/m(2)), arm diameter (28.9 +/- 8.9 cm), and arm skinfold (2.5 +/- 0.7 cm), was normal. A positive correlation was found between IGF1 at visit 1 and the lowest BMD for hip, spine, or radius (r = 0.39, P = 0.04). High sensitive C-reactive protein (hsCRP) and leukocytes were higher at the fracture event compared to 5 weeks later (P = 0.07 and P amp;lt; 0.001, respectively). Fracture healing parameters (i.e. callus formation, fracture line, and stage of union) were positively correlated with the initial leukocyte count and to difference in thrombocyte count between visit 1 and 3.

    Conclusions

    In elderly women with low-energy distal radius fractures, an association between IGF1 and lowest measures of BMD was found, indicating that low IGF1 could be an indirect risk factor for fractures. Fracture healing was associated with initial leukocytosis and a lower thrombocyte count, suggesting that inflammation and thrombocytes are important components in fracture healing.

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