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Oxycodone is a strong opioid drug commonly used to treat acute, cancer, and chronic non-malignant pain. In this study, all oxycodone-related medico-legal cases where death had occurred in a hospital or nursing home in Finland were investigated to determine the range of post-mortem (PM) oxycodone blood concentrations in a therapeutic setting. All toxicology cases in which oxycodone was detected in PM femoral blood during the 4-year period of 2016–2019 in Finland were retrieved from the national PM toxicology database. In this material, the 365 deceased hospital patient cases that met the study inclusion criteria were divided into four groups according to the cause and manner of death. The reference group of 121 fatal oxycodone poisoning cases comprised two groups: those with verified associated drug abuse and those without drug abuse. The median oxycodone concentration in PM blood was significantly higher in cancer patients (0.10 mg/L) than in patients with recent surgery (0.07 mg/L) or other disease (0.06 mg/L) (p p

Informed consent is based on basic ethical principles that should be considered when conducting biomedical and behavioral research involving human subjects. These principles—respect, beneficence, and justice—form the foundations of informed consent which in itself is grounded on three fundamental elements: information, comprehension, and voluntary participation. While informed consent has focused on human subjects and research, the practice has been adopted willingly in the forensic science arena primarily to acquire reference samples from family members to assist in identifying missing persons. With advances in molecular biology technologies, data mining, and access to metadata, it is important to assess whether the past informed consent process and in particular associated risks are concomitant with these increased capabilities. Given the state-of-the-art, areas in which informed consent may need to be modified and augmented are as follows: reference samples from family members in missing persons or unidentified human remains cases; targeted analysis of an individual(s) during forensic genetic genealogy cases to reduce an investigative burden; donors who provide their samples for validation studies (to include population studies and entry into databases that would be applied to forensic statistical calculations) to support implementation of procedures and operations of the forensic laboratory; family members that may contribute samples or obtain genetic information from a molecular autopsy; and use of medical and other acquired samples that could be informative for identification purposes. The informed consent process should cover (1) purpose for collection of samples; (2) process to analyze the samples (to include type of data); (3) benefits (to donor, target, family, community, etc. as applicable); (4) risks (to donor, target, family, community, etc. as applicable); (5) access to data/reports by the donor; (6) sample disposition; (7) removal of data process (i.e., expungement); (8) process to ask questions/assessment of comprehension; (9) follow-up processes; and (10) voluntary, signed, and dated consent. Issues surrounding these topics are discussed with an emphasis on addressing risk factors. Addressing informed consent will allow human subjects to make decisions voluntarily and with autonomy as well as secure the use of samples for intended use.

Military pilots undergo rigorous selection compared with civilian professional pilots because of different operational requirements. There are no studies of military pilots’ subsequent civil aviation careers and fatal pilot aviation accidents. This study focuses on Vietnam War (VW) pilots and subsequent fatal aviation accidents in the U.S from 1965 to 2018. In total nine aviation accidents met the inclusion criteria and are described in detail, including the pilots’ previous civil aviation incidents. The VW pilots were healthy, had valid Medicals and continued to fly in demanding pilot positions after their military careers. Although the data are limited, this study suggests that previous military pilots may differ slightly from other pilots in their subsequent civil aviation careers. publishedVersion

Inpatients have a particular risk of sustaining medical adverse events (MAEs). This analysis aimed to identify patterns of change in deaths due to MAEs among US inpatients. The analysis was based on nationwide cause-of-death data from 1999 to 2019. To adjust for secular trends in overall mortality, MAE deaths were examined proportional to total deaths. Statistical analysis was performed by means of joinpoint regression modeling. Over the analysis period, a total of 18,126,135 certified deaths occurred among inpatients. MAEs were used as the underlying cause of death in 43,899 cases (0.24%). MAE deaths showed a significant increase from mid-2010s onwards; the estimated increase in MAE deaths was up to 15.6% per year (95% confidence interval 11.3–20.1) from 2014 to 2019. Procedure-related events mainly drove the trend. As the present data are insufficient to substantiate and disentangle underlying factors, future analyses are warranted.

Laboratories and their criminal justice systems are confronted with challenges for implementing new technologies, practices, and policies even when there appears to be demonstrative benefits to operational performance. Impacting decisions are the often higher costs associated with, for example, new technologies, limited current budgets, and making hard decisions on what to sacrifice to take on the seemingly better approach. A prospective cost–benefit analysis (CBA) could help an agency better formulate its strategies and plans and more importantly delineate how a relatively small increase to take on, for example, a new technology can have large impact on the system (e.g., the agency, other agencies, victims and families, and taxpayers). To demonstrate the process and potential value a CBA was performed on the use of an alternate and more expensive swab with reported better DNA yield and being certified human DNA free (i.e., nylon 4N6FLOQSwabs®), versus the traditional less costly swab (i.e., cotton swab). Assumptions are described, potential underestimates and overestimates noted, different values applied (for low and modest to high), and potential benefits (monetary and qualitative) presented. The overall outcome is that the cost of using the more expensive technology pales compared with the potential tangible and intangible benefits. This approach could be a guide for laboratories (and associated criminal justice systems) worldwide to support increased funding, although the costs and benefits may vary locally and for different technologies, practices, and policies. With well-developed CBAs, goals of providing the best services to support the criminal justice system and society can be attained.

Although knee measurements yield high classification rates in metric sex estimation, there is a paucity of studies exploring the knee in artificial intelligence-based sexing. This proof-of-concept study aimed to develop deep learning algorithms for sex estimation from radiographs of reconstructed cadaver knee joints belonging to the Terry Anatomical Collection. A total of 199 knee radiographs were obtained from 100 skeletons (46 male and 54 female cadavers; mean age at death 64.2 years, range 50-102 years) whose tibiofemoral joints were recon-structed in standard anatomical position. The AIDeveloper software was used to train, validate, and test neural network architectures in sex estimation based on image classification. Of the explored algorithms, an MhNet-based model reached the highest overall testing accuracy of 90.3%. The model was able to classify all females (100.0%) and most males (78.6%) correctly. These preliminary findings encourage further research on artificial intelligence-based methods in sex estimation from the knee joint. Combining radiographic data with automated and externally validated algorithms may establish valuable tools to be utilized in forensic anthropology.

Objectives Gunshot wounds are frequently studied using computed tomography (CT) to examine tissue damage. In this study, we aimed to test the potential of post-mortem CT (PMCT) in shooting distance estimation at distances 0–100 cm. We hypothesized that in addition to the wound channel, we could also potentially detect tissue damage caused by muzzle pressure on PMCT. Results A total of 59 gunshot wounds (23 contact shots, 21 close-range shots, 15 distant shots) were inflicted on eight piglet carcasses with a .22 Long Rifle handgun. PMCT scans were obtained using clinical equipment, and they were evaluated for wound characteristics by visual inspection and numeric measurements. In our data, contact shots could be clearly distinguished from close-range and distant shots by a hyperdense ring-shaped area surrounding the outermost part of the wound channel. Close-range and distant shot wounds did not have this feature and were difficult to distinguish from each other. The mean wound channel diameter ranged from 3.4 to 5.4 mm, being smallest in contact shots and largest in distant shots. These preliminary findings suggest that PMCT may aid the estimation of shooting distance. As this study only addressed low velocity gunshot wounds in carcasses, further studies are warranted.

Background: Physical activity (PA) is a determinant of insulin sensitivity. It is more unclear how sedentary behavior (SB) and patterns of SB associate with insulin sensitivity. Purpose: To determine how SB, breaks in sitting, standing, PA, and fitness are associated with insulin sensitivity in adults with metabolic syndrome. Methods: Sixty-four sedentary adults with metabolic syndrome (mean age 58 years; 37 women) were included. SB, breaks in sitting, standing, and PA were measured for four weeks with accelerometers. VO2max was measured with maximal cycle ergometry. Insulin sensitivity was determined by hyperinsulinaemic-euglycaemic clamp (M-value) and fasting blood sampling (HOMA-IR, insulin). Multivariable regression was used for analyses. Results: Sedentary time, standing, steps, and VO2max were associated with M-value, HOMA-IR, and insulin, while breaks in sitting associated only with M-value. When adjusted for body fat %, only standing remained significantly associated with HOMA-IR and insulin, and significance was maintained even when further adjusted for PA, SB, and fitness (all p-values, The Health & Fitness Journal of Canada, Vol. 14 No. 3 (2021): Proceedings from the 8th International Society for Physical Activity and Health Congress

Background: Quantitative changes in the cardiac autonomic nervous system may play an important role in the pathogenesis of various cardiovascular diseases. In the present morphological analysis, we aimed to study autonomic nerve density in myocardial sleeves and surrounding fibro-fatty tissue around caval veins. We correlated the nerve distribution with cardiovascular mortality and a history of atrial fibrillation. Materials and Methods: A total of 24 autopsied adult hearts were excised together with the superior and inferior vena cava and grouped according to the immediate and underlying causes of death (cardiovascular vs. non-cardiovascular), and documented heart rhythm history (atrial fibrillation vs. sinus rhythm). The density of autonomic nerves was quantified by measuring the area of immunohistochemical staining for sympathetic (tyrosine hydroxylase, TH) and parasympathetic (choline acetyltransferase, CHAT) nerves and ganglia. Growth-associated protein 43 (GAP43) was used as a neural growth marker. Results: The mean density of TH-positive nerves in the superior vena cava myocardial sleeves was significantly decreased between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean density ± standard deviation (SD): 704.81±1016.41 µm2/mm2 vs. 2391.01±1841.37 µm2/mm2; P =.008). Similarly, the nerve density of GAP43-positive nerves in the superior vena cava myocardial sleeves was significantly lower in subjects with documented underlying cardiovascular cause of death (mean density ± SD: 884.74±1240.16 µm2/mm2 vs. 2132.89±1845.89 µm2/mm2; P =.040). The mean age was significantly higher in subjects with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean age ± SD: 69.2±11.9 years, vs. 57.5±11.2 years, P =.016). No differences were found in nerve densities of TH-positive (953.01±1042.93 µm2/mm2 vs. 919.26±1677.58 µm2/mm2), CHAT-positive (180.8±532.9 µm2/mm2 vs. 374.22±894.76 µm2/mm2), and GAP43-positive nerves (593.58±507.97 µm2/mm2 vs. 1337.34±1747.69 µm2/mm2) in myocardial sleeves around the inferior vena cava between groups with documented immediate cardiovascular vs. non-cardiovascular cause of death. Similarly, no differences were found between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (TH: 717.23±887.31 µm2/mm2 vs. 1365.51±2149.10 µm2/mm2; CHAT: 256.18±666.86 µm2/mm2 vs. 368.53±959.47 µm2/mm2; GAP43: 661.21±839.51 µm2/mm2 vs. 1759.90±2008.80 µm2/mm2). Moreover, there was no association found in nerve densities between subjects with documented atrial fibrillation vs. sinus rhythm (TH: 235.07±425.69 µm2/mm2 vs. 1166.08±1563.84 µm2/mm2; CHAT: 648.59±1017.33 µm2/mm2 vs. 175.31±641.65 µm2/mm2; GAP43: 990.17±1315.18 µm2/mm2 vs. 1039.86±1467.23 µm2/mm2). Conclusions: Decrease of superior vena cava myocardial sleeve sympathetic nerves may be associated with cardiovascular mortality and/or aging. No difference in autonomic innervation was found between subjects with documented atrial fibrillation vs. sinus rhythm. publishedVersion

The medical autopsy (also called hospital or clinical autopsy) is a highly specialised medical procedure, which requires professional expertise and suitably equipped facilities. To ensure high standards of performance, the Working Group of Autopsy Pathology of the European Society of Pathology (ESP) suggests a code of practice as a minimum standard for centres performing medical autopsies. The proposed standards exclusively address autopsies in adults, and not forensic autopsies, perinatal/or paediatric examinations. Minimum standards for organisation, standard of premises, and staffing conditions, as well as minimum requirements for level of expertise of the postmortem performing specialists, documentation, and turnaround times of the medical procedure, are presented. Medical autopsies should be performed by specialists in pathology, or by trainees under the supervision of such specialists. To maintain the required level of expertise, autopsies should be performed regularly and in a number that ensures the maintenance of good practice of all participating physicians. A minimum number of autopsies per dedicated pathologist in a centre should be at least 50, or as an average, at least one autopsy per working week. Forensic autopsies, but not paediatric/perinatal autopsies may be included in this number. Turnaround time for final reports should not exceed 3 weeks (14 working days) for autopsies without fixation of brain/spinal cord or other time-consuming additional examinations, and 6 weeks (30 working days) for those with fixation of brain/spinal cord or additional examinations.

Background: Insulinoma-associated protein 1 (INSM1) has been considered as a novel immunostain for neuroendocrine tumors (NETs) and is hypothesized to be more reliable than first-generation NET biomarkers, such as CGA (chromogranin A), SYP (synaptophysin) and CD56 (neural cell adhesion molecule). In this review, we summarize existing literature on INSM1′ s reliability as an immunostain for detection of various NETs, its results in comparison to first-generation NET biomarkers, and its expression in both non-NETs and benign tissues/cells on cytology specimens (cell blocks/smears). publishedVersion

Aims To determine trends in 3,4 methylenedioxymethamphetamine (MDMA)-related death rates across Australia, Finland, Portugal and Turkey and to analyse causes of death across countries; and 3. analyse the toxicology of deaths across countries. Design Analysis of MDMA-related deaths extracted from a national coronial database in Australia (2001-2019) and national forensic toxicology databases in Finland (2001-2017), Portugal (2008-2019) and Turkey (2007-2017). Presentation of MDMA use and seizure data (market indicators). Setting Australia, Finland, Portugal and Turkey. Cases All deaths in which MDMA was considered by the forensic pathologist to be contributory to death. Measurements Information collected on cause and circumstances of death, demographics, and toxicology. Findings 1,400 MDMA-related deaths were identified in Turkey, 507 in Australia, 100 in Finland, and 45 in Portugal. The median age ranged from 24 to 27.5 years and males represented between 81 and 95% of the deaths across countries. Standardised mortality rates significantly increased across all four countries from 2011-2017, during a period of increased purity and availability of MDMA. The underlying cause of death was predominantly due to drug toxicity in Australia (n=309, 61%), Finland (n=70, 70%) and Turkey (n=840, 60%), and other causes in Portugal (n=25, 56%). Minorities of all deaths across the countries were due to MDMA toxicity alone (13-25%). These deaths had a significantly higher blood MDMA concentration than multiple drug toxicity deaths in Australia, Finland and Turkey. Drugs other than MDMA commonly detected were stimulants (including cocaine, amphetamine and methamphetamine) (Australia 52% and Finland 61%) and alcohol (Australia 46% and Portugal 49%). In addition to MDMA toxicity, benzodiazepines (81%) and opioids (64%) were commonly identified in these deaths in Finland. In comparison, synthetic cannabinoids (15%) and cannabis (14%) were present in a minority of deaths in Turkey. Conclusions Deaths related to 3,4 methylenedioxymethamphetamine (MDMA) increased in Australia, Finland, Portugal and Turkey between 2011 and 2017. MDMA toxicity alone can be fatal but multiple drug toxicity remains more prevalent.

Background Longitudinal studies demonstrate an average decline in physical activity (PA) from adolescence to young adulthood. However, while some subgroups of adolescents decrease activity, others increase or maintain high or low activity. Activity domains may differ between subgroups (exhibiting different PA patterns), and they offer valuable information for targeted health promotion. Hence, the aim of this study was to identify PA patterns from adolescence to young adulthood; also to explore the associations of (i) changes in PA domains and in sedentary time, (ii) sociodemographic factors, and (iii) self-rated health with diverging PA patterns. Methods The observational cohort study data encompassed 254 adolescents at age 15 and age 19. K-means cluster analysis for longitudinal data was performed to identify participant clusters (patterns) based on their accelerometry-measured moderate-to-vigorous PA (MVPA). Logistic regressions were applied in further analysis. Results Five PA patterns were identified: inactivity maintainers (n = 71), activity maintainers (n = 70), decreasers from moderate (to low) PA (n = 61), decreasers from high (to moderate) PA (n = 32), and increasers (n = 20). At age 15, participation in sports clubs (SC, 41–97%) and active commuting (AC, 47–75%) was common in all the patterns. By age 19, clear dropout from these activities was prevalent (SC participation mean 32%, AC 31–63%). Inactivity maintainers reported the lowest amount of weekly school physical education. Dropout from SC – in contrast to non-participation in SC – was associated with higher odds of being a decreaser from high PA, and with lower odds of being an inactivity maintainer. Maintained SC participation was associated with higher odds of belonging to the decreasers from high PA, and to the combined group of activity maintainers and increasers; also with lower odds of being an inactivity maintainer. Maintenance/adoption of AC was associated with decreased odds of being an inactivity maintainer. Self-reported health at age 19 was associated with the patterns of maintained activity and inactivity. Conclusions PA patterns diverge over the transition to adulthood. Changes in SC participation and AC show different associations with diverging PA patterns. Hence, tailored PA promotion is recommended. Supplementary Information The online version contains supplementary material available at 10.1186/s12966-021-01130-x.

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Publisher Copyright: Copyright © 2021 Vuorio, Kovanen, Budowle, Sajantila, Palo and Stoop. Despite the increased frequency and scale of wildfire-related catastrophes, there has been little or no effective and coordinated international policy to address their highly negative impact. Possibly a generalized approach to respond to such major events could be modeled on existing international safety investigation policies and agreements that already have proved successful. The International Civil Aviation Organization (ICAO) outlines safety investigations after international fatal aviation accidents. Although this well-established safety investigation protocol cannot be directly applied in acute wildfire-related accidents, it can offer a useful framework for establishing international guidelines to reduce risk of future wildfire catastrophes. The co-operation between safety investigation authorities has been shown to be fruitful especially for those less developed countries that have limited resources and experience related to accident investigations. While primarily an adaptive measure that can set practices to reduce vulnerability and fragility of ecosystems and human societies, the same policies could be seen as a climate change mitigation measure, as wildfires can contribute significantly to global CO2 emissions. Finally, the concept of independent and qualified safety investigations represents the principle of serendipity: disclosing by accident something that has not been foreseen. Feedback from reality compensates assumptions and limitations of feedforward analysis of complex systems that can only reveal their dynamics and performance in reality and over time.

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

Little is known about the potential of artificial intelligence in forensic shotgun pattern interpretation. As shooting distance is among the main factors behind shotgun patterning, this proof-of-concept study aimed to explore the potential of neural net architectures to correctly classify shotgun pattern images in terms of shooting distance. The study material comprised a total of 106 shotgun pattern images from two discrete shooting distances (n = 54 images from 10 m and n = 52 images from 17.5 m) recorded on blank white paper. The dataset was used to train, validate and test deep learning algorithms to correctly classify images in terms of shooting distance. The open source AIDeveloper software was used for the deep learning procedure. In this dataset, a TinyResNet-based algorithm reached the highest testing accuracy of 94%. Of the testing set, the algorithm classified all 10 m patterns correctly, and misclassified one 17.5 m pattern. On the basis of these preliminary data, it seems achievable to develop algorithms that would serve as a beneficial tool for forensic investigators when estimating shooting distances from shotgun patterns. In the future, studies with larger and more complex datasets are needed to develop robust and applicable algorithms for forensic shotgun pattern interpretation.

This article examines clinical practice guidelines (CPG) in the courtroom. The guidelines in question are Finnish national current care guidelines for brain injuries, and the case context is traffic insurance compensation cases contested in the Helsinki district court. We analyse 11 case verdicts qualitatively, drawing from earlier sociological and theoretical accounts of clinical practice guidelines and evidence-based medicine. What makes the case-type relevant for studying clinical practice guidelines is the fact that the cases, which feature a medical dispute concerning traumatic brain injury, involve highly specialized expertise and contradictory expert claims, but the cases are decided in a generalist court by non-expert judges. What we show in the article is how the guidelines structure, sequence and initiate temporal reworking in the judges' representation of medical evidence and testimony, and how the plaintiffs' delayed diagnoses complicate the application of the CPG in the evaluation. We further discuss the guidelines’ epistemic authority in the verdicts and finish by comparing the 2008 and 2017 editions of Finnish CPGs for brain injuries, suggesting a multifaceted, courtroom-mediated feedback loop between the patient-plaintiffs and the clinical practice guidelines. publishedVersion

Sex estimation is an important part of osteological analysis of skeletons and forensic identification process. Traditionally cranial and pelvic traits are utilized for accurate sex estimation. However, post-cranial measurements have also been proven to accurately estimate sex especially from robust bones such as the femur. In this study, we investigated the potential of knee breadth dimensions in sex estimation in a Finnish population. To conduct this study we utilized a study sample (n=1654) belonging to the Northern Finland Birth Cohort 1966. All individuals were 46 years of age at the time of the examination. Three knee breadth dimensions were measured from subjects' knee posteroanterior radiographs: femoral biepicondylar breadth (FBEB), mediolateral breadth of the femoral condyles (FCML), and mediolateral breadth of the tibial plateau (TPML). Sex estimation was performed using logistic regression. The study clearly demonstrated that all three measurements were different between males and females. Sectioning points for individual knee breadth measurements were 82.9 mm for FBEB, 76.6 mm for FCML and 75.4 mm for TPML. The classification rates ranged from 90.9% to 93.6%. The less commonly used measurements of FCML and TPML showed higher accuracy than FBEB in sex estimation. Our study confirmed that knee breadths can be successfully utilized to improve sex estimation in cases where the skeleton is only partially preserved and other major components of sex estimation are absent. We can also provide new standards for sex estimation from the knee joint in a Finnish population. Sex estimation is an important part of osteological analysis of skeletons and forensic identification process. Traditionally cranial and pelvic traits are utilized for accurate sex estimation. However, post-cranial measurements have also been proven to accurately estimate sex especially from robust bones such as the femur. In this study, we investigated the potential of knee breadth dimensions in sex estimation in a Finnish population. To conduct this study we utilized a study sample (n=1654) belonging to the Northern Finland Birth Cohort 1966. All individuals were 46 years of age at the time of the examination. Three knee breadth dimensions were measured from subjects' knee posteroanterior radiographs: femoral biepicondylar breadth (FBEB), mediolateral breadth of the femoral condyles (FCML), and mediolateral breadth of the tibial plateau (TPML). Sex estimation was performed using logistic regression. The study clearly demonstrated that all three measurements were different between males and females. Sectioning points for individual knee breadth measurements were 82.9 mm for FBEB, 76.6 mm for FCML and 75.4 mm for TPML. The classification rates ranged from 90.9 % to 93.6 %. The less commonly used measurements of FCML and TPML showed higher accuracy than FBEB in sex estimation. Our study confirmed that knee breadths can be successfully utilized to improve sex estimation in cases where the skeleton is only partially preserved and other major components of sex estimation are absent. We can also provide new standards for sex estimation from the knee joint in a Finnish population.

Publisher Copyright: © 2021 The Author(s) Propranolol is a widely used beta-blocker mainly prescribed for the treatment of hypertension and other cardiac conditions. This medicine is also a frequent finding in drug screens, but little is known about its post-mortem toxicological profile. Our aim was to examine all post-mortem toxicology cases positive for propranolol in a three-year period, between 2016 and 2018 in Finland, and to compare these cases to those positive for metoprolol, another beta-blocker commonly used to treat cardiac diseases. There were 179 cases positive for propranolol and 416 for metoprolol in the study period. In the majority of propranolol cases (53%), the drug concentration in the blood was above the typical therapeutic range, but among the metoprolol cases this proportion was 18%. Propranolol was significantly more common than metoprolol in fatal poisonings, suicides and in cases with a history of drug abuse. Alcohol, benzodiazepines, antipsychotics and antidepressants were significantly more often detected in propranolol cases than in metoprolol cases. The deceased positive for propranolol were significantly younger than those positive for metoprolol. Cardiovascular diseases as the underlying cause of death were significantly more common among the metoprolol cases than among the propranolol cases. Our results showed significant differences between the propranolol group and the metoprolol group in post-mortem toxicology cases. The two drugs were used by two very different groups of people, with propranolol use being associated with psychiatric conditions.

Medical devices must be tested before marketing in accordance with ISO EN 10993-10 in order to avoid skin sensi­tization. This standard predominantly refers to the in vivo test but does not exclude the use of in vitro methods that have been sufficiently technically and scientifically validated for medical device testing. It is foreseen that, due to the complexity of the sensitization endpoint, a combination of several methods will be needed to address all key events occurring in the sensitization process. The objective of this pilot study was to evaluate the sensitization potential of selected medical devices using a combination of in chemico (DPRA, OECD TG 442C) and in vitro (LuSens, OECD TG 442D) methods in comparison with the in vivo (LLNA DA, OECD TG 442A) method and to suggest a possible testing strategy for the safety assessment of medical device extracts. Overall, one of the 42 tested samples exhibited positive results in all employed test methods, while 33 samples were predicted as non-sensitizing in all three performed methods. This study demonstrated good agreement between in vitro and in vivo results regarding non-sensitizing samples; however, some discrepancies in positive classification were recorded. A testing strategy is suggested in which negative results are accepted and any positive results in the in chemico or in vitro tests are followed up with a third in vitro test and evaluated in accordance with the “2 out of 3 approach”. This strategy may reduce and replace animal use for testing the sensitization potential of medical devices. publishedVersion

Background: Multisite pain is commonly chronic and often lacks its initial role as a potential tissue damage signal. Chronic pain among working-age individuals is a risk for disability and imposes a major burden on health care systems and society. As effective treatments for chronic pain are largely lacking, better identification of the factors associated with pain over working years is needed. Methods: Members of the Northern Finland Birth Cohort 1966 participated in data collection at the ages of 31 (n = 4,028) and 46 (n = 3,429). Using these two time points, we performed a multivariable analysis of the association of socioeconomic, occupational, psychological and lifestyle factors (i.e., low education, living alone, low household income, unemployment, occupational physical exposures [hard physical labor, leaning forward, back twisting, constant moving, lifting loads of ≥ 1 kg], physical inactivity, regular smoking, regular drinking, overweight, and psychiatric symptoms) with the number of musculoskeletal pain sites (i.e., upper extremity, lower extremity, lower back, and the neck-shoulder region; totalling 0–4 pain sites). The data were analyzed using generalized estimating equations. Results: At the age of 31, multisite pain was reported by 72.5% of men and 78.6% of women. At the age of 46, the prevalence of multisite pain was 75.7% among men and 82.7% among women. Among men, the number of pain sites was positively associated with age (rate ratio 1.05, 95% confidence interval 1.01–1.08), low household income (1.05, 1.01–1.08), unemployment (1.13, 1.06–1.19), any occupational exposure (1.17, 1.12–1.22), regular smoking (1.06, 1.02–1.11), and psychiatric symptoms (1.21, 1.17–1.26). Among women, the number of pain sites was positively associated with age (1.06, 1.04–1.10), unemployment (1.10, 1.05–1.15), any occupational exposure (1.10, 1.06–1.13), regular smoking (1.06, 1.02–1.10), overweight (1.08, 1.05–1.11), and psychiatric symptoms (1.19, 1.15–1.22); living alone was negatively associated with the number of pain sites (0.95, 0.91–0.99). Conclusion: Of the studied predictors, psychiatric symptoms, occupational physical exposures and unemployment were most strongly associated with multisite pain among both sexes. The results of this study deepen the understanding of the underlying factors of and comorbidities behind multisite pain, and help develop pain relief and rehabilitation strategies for working-age individuals with multisite pain.

Fascin 1 plays important pro-metastatic roles in head and neck carcinoma (HNSCC) migration, invasion, and metastasis. However, limited advancement in targeting metastasis remains a major obstacle in improving HNSCC patients’ survival. Therefore, we assessed the therapeutic potential of fascin 1 targeted inhibition and its potential prognostic value in HNSCC patients. Using in vitro and in vivo approaches, we investigated the effect of compound G2, a novel fascin 1 inhibitor, on HNSCC cells migration, invasion, and metastasis. High-throughput screening (HTS) was used to assess cytotoxic activity of compound G2 alone or combined with irradiation. We also evaluated the prognostic potential of fascin 1 in HNSCC patients. Interestingly, compound G2 reduced carcinoma cells migration and invasion in vitro and inhibited metastasis in vivo. Moreover, HTS revealed a modest cytotoxic activity of the compound G2 on HNSCC cell lines. Irradiation did not synergistically enhance the compound G2-mediated cytotoxic activity. Survival analyses showed that high fascin 1 immunoexpression, at the tumor invasive front, was associated with cancer-specific mortality in the advanced stages of HNSCC. Collectively, our findings suggest that fascin 1 represents a promising anti-metastatic therapeutic target and a useful prognostic marker in patients with HNSCC. Novel anti-metastatic agents could provide a valuable addition to cancer therapy. publishedVersion

Highlights • Northern Finnish women had lower risks of any death and unnatural death than men. • After early life, the unnatural mortality of men was 3–5 times that of women. • Accident and suicide mortality rates of men were ≥ 2 times those of women. • Homicides were rare among either sex., The Finnish population has a long life expectancy but ranks high in unnatural deaths on the European scale. Mortality has historical regional discrepancy in Finland, as Northern Finns are overrepresented in both natural and unnatural deaths. This study aimed to characterize the age- and sex-related trends in unnatural mortality among Northern Finns. Altogether 12 143 individuals, constituting >95% of births in Northern Finland in 1966, were followed up for a median of 52 years. The mortality patterns of this population were studied using death record data. Crude annual mortality rates were calculated and graphed for 10-year age strata (all-cause, natural-cause, and unnatural-cause mortality, as well as accident, suicide, and homicide mortality). Cox regression was used to analyze the sex discrepancy in mortality. A total of 874 deaths (7.2%) occurred during the follow-up period. Women had 47% and 73% lower risks of any death and unnatural death than men, respectively. From the second decade of life onwards, the unnatural mortality of men was 3–5 times that of women. Accident and suicide mortality rates of men were 2–13 and 2–3 times those of women, respectively. Homicides were rare among either sex. We conclude that Northern Finnish women have a substantially lower risk of all-cause mortality and unnatural mortality than men. To aid the development of preventive strategies, future studies should aim to identify the underlying factors behind unnatural mortality. Primarily, emphasis should be placed on the increased mortality of men from the second decade of life onwards.

A lot has been published on the anticipated effects of the current COVID-19 pandemic on users of illegal drugs. In this study, we present evidence-based data on such effects, namely, the increased number of drug findings in post-mortem investigations. All post-mortem toxicology cases positive for at least one of the following: buprenorphine, amphetamine or cannabis, were investigated in the first 8 months of the year 2020, and the monthly numbers were compared to those in the previous 5 years from 2015 to 2019. These substances served as indicator analytes that could reveal changes in the drug using population. Right after the government restrictions came into force in March 2020, the numbers of buprenorphine, amphetamine and cannabis findings increased. The increase was most noticeable for amphetamine and was evident in all age groups. Our findings indicate that the assumptions on the increased risk of drug-related harm (including death) have become reality. Reduced access to harm-reduction services seems to have increased the mortality among individuals that use buprenorphine, amphetamine or cannabis. Significant and prompt actions need to be taken in order to find new ways in helping this vulnerable group of people. Non

We present a case of an accidental fatal fentanyl overdose caused by increased uptake of the drug from a transdermal patch while experiencing the heat of a sauna. The transdermal patch administers fentanyl at a relatively constant rate through the skin. However, in the subcutaneous tissue, blood circulation greatly influences the rate of this drug's systemic intake. In the present case, an elderly woman with multiple health conditions was prescribed fentanyl patches but was unaware of the risks associated with external heat sources when one wears the patch. She was found dead in the sauna with a postmortem femoral blood concentration of fentanyl that was elevated (15 mu g/L). The cause of death was determined to be fatal poisoning by fentanyl with the contributing factor of external heat from the sauna. Risks associated with transdermal administration of a potent opioid-like fentanyl are widely described in the scientific literature and described in the manufacturer's summary of product characteristics. Physicians and pharmacists should take particular care to ensure that patients understand these risks. Non

The COVID-19 pandemic has forced forensic practitioners to consider how we perform our normal duties, especially when those duties involve humans. The potential for contracting the virus from working in close contact with living sufferers is high, and we have yet to fully determine the risk of infection from the deceased. In an attempt to support the community, the Journal of Forensic & Legal Medicine has drawn together three articles which underline the importance of continued forensic medical practice during the pandemic and highlight some factors to consider in a Roadmap towards safe practice. Our Roadmap has intentionally taken an international perspective and supports other work we have published in the Journal on our collective response to the COVID-19 crisis.

Subclinical psychosis, including schizotypal indicators and psychotic experiences, predicts future suicidal ideation. This relationship may reflect unmeasured confounding from environmental factors, genetic factors, or both. We used a genetically-informative twin design to understand if the association between subclinical psychosis and suicidal ideation is independent of shared genetic and environmental factors. We analysed cross-sectional associations of age-22 self-reported subclinical psychosis (positive, negative, and disorganised features) with suicidal ideation in twins participating in the FinnTwin12 study (maximum n = 1213). Then, we analysed the reverse association of age-14 suicidal ideation with age-22 subclinical psychosis. Associations were studied first among individuals and then within monozygotic (MZ) and dizygotic (DZ) pairs. Individual-level analyses showed that all subclinical psychosis factors were associated with suicidal ideation. In within-pair analyses, estimates of associations were lower for MZ pairs than DZ pairs, except for the negative schizotypy-suicidal ideation association where estimates were consistent across individual-level and within-pair analyses. Findings provide evidence that the association between negative features and suicide ideation is not explained by familial factors and may be causal, though the possibility of confounding by individual-specific environmental factors and reverse causation cannot be ruled out. The relationships of positive and disorganised subclinical psychosis features with suicidal ideation cannot be explained by confounding due to environmental factors shared between siblings, but their associations may be due to shared genetic factors. (C) 2020 Elsevier B.V. All rights reserved.

Background Buprenorphine is abused in several countries notwithstanding its benefits as an analgesic and as an opioid agonist treatment medication. Benzodiazepines and alcohol have previously been associated with buprenorphine toxicity. This study elucidates the role of emerging concomitant drugs in different groups of buprenorphine user deaths. Methods All cases in the Finnish national post-mortem toxicology database from 2016–2019 in which buprenorphine or norbuprenorphine was a laboratory finding in any post-mortem specimen and age at death of 15–64 years were investigated for cause and manner of death, concurrent drug and alcohol findings, age, and gender. Results There were 792 deaths with a buprenorphine finding, of which buprenorphine was implicated in poisoning without other opioids in 271 cases (34 %). In this group of buprenorphine poisoning deaths, concomitant benzodiazepines were found in 94 % (clonazepam 53 %), illicit drugs in 63 %, gabapentinoids in 50 % (pregabalin 41 %), alcohol in 41 %, antidepressants in 32 %, and antipsychotics in 28 % of cases; only three deaths showed no benzodiazepines, alcohol, or gabapentinoids. Polydrug use was common regardless of the cause of death. In the age group 15 to 24 years, concomitant use of benzodiazepines and illicit drugs, and buprenorphine poisoning were more prevalent than in the age group 25–64 years. Conclusions The unprecedentedly high concomitant use of benzodiazepines in buprenorphine user deaths obscures other possible pharmacological risk factors for buprenorphine poisoning that could be relevant for prevention. Higher mortality in the younger age group suggests particularly unsafe drug use patterns that should be addressed.

This study is the seventh report on fatal poisonings among drug addicts in the Nordic countries. In this report, we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on gender, number of deaths, places of deaths, age, main intoxicants and substances detected in blood were recorded to obtain national and comparable Nordic data, and to allow comparison with earlier studies conducted in 1984, 1991, 1997, 2002, 2007 and 2012. The death rate (number of deaths per 100,000 inhabitants) was highest in Iceland (6.58) followed closely by Sweden (6.46) and then lowest in Denmark (4.29). The death rate increased in Finland (5.84), Iceland and Sweden and decreased in Denmark compared to earlier studies. The death rate in Norway, which has decreased since 2002, has stabilised around 5.7 as of 2017. Women accounted for 7-23% of the fatal poisonings. The percentage was lowest in Iceland and highest in Finland and Norway. The age range was 14-70 years. The median age (41 years) was highest in Denmark and Norway. The other countries had a median age between 33 and 35 years. Opioids were the main cause of death. Methadone remained the main intoxicant in Denmark, while heroin/morphine was still the main intoxicant in Norway, as was buprenorphine in Finland. However, the picture has changed in Sweden compared to 2012, where heroin/morphine caused most deaths in 2017. Sweden also experienced the highest number of deaths from fentanyl analogues (67 deaths) and buprenorphine (61 deaths). Deaths from fentanyl analogues also occurred in Denmark, Finland and Norway, but to a smaller extent. Over the years, the proportion of opioid deaths has decreased in all countries except Sweden, which has experienced an increase. This decline has been replaced by deaths from CNS stimulants like cocaine, amphetamine and methylenedioxymethamphetamine (MDMA). Cocaine deaths have occurred in all countries but most frequently in Denmark. MDMA deaths have increased in all countries but mostly in Finland. Poly-drug use was widespread, as seen in the earlier studies. The median number of detected drugs per case varied from 4-6. Heroin/morphine, methadone, buprenorphine, cocaine, amphetamine, methamphetamine, MDMA, tetrahydrocannabinol (THC) and benzodiazepines were frequently detected. Pregabalin and gabapentin were detected in all countries, especially pregabalin, which was detected in 42% of the Finnish cases. New psychoactive substances (NPS) occurred in all countries except Iceland. (C) 2020 Elsevier B.V. All rights reserved.

The imprints left by persistent DNA viruses in the tissues can testify to the changes driving virus evolution as well as provide clues on the provenance of modern and ancient humans. However, the history hidden in skeletal remains is practically unknown, as only parvovirus B19 and hepatitis B virus DNA have been detected in hard tissues so far. Here, we investigated the DNA prevalences of 38 viruses in femoral bone of recently deceased individuals. To this end, we used quantitative PCRs and a custom viral targeted enrichment followed by next generation sequencing. The data was analyzed with a tailor-made bioinformatics pipeline. Our findings revealed bone to be a much richer source of persistent DNA viruses than earlier perceived, discovering ten additional ones, including several members of the herpesand polyomavirus families, as well as human papillomavirus 31 and torque teno virus. Remarkably, many of the viruses found have oncogenic potential and/or may reactivate in the elderly and immunosuppressed individuals. Thus, their persistence warrants careful evaluation of their clinical significance and impact on bone biology. Our findings open new frontiers for the study of virus evolution from ancient relics as well as provide new tools for the investigation of human skeletal remains in forensic and archaeological contexts.

Background Satisfaction is a major element in assessing quality of care. It has decreased in Finland in recent decades as well as continuity of care. We investigated which demographic, health-related, and local health care service factors, especially continuity of care, are associated with the population’s satisfaction with local health care services. Methods The data are part of the Health and Social Support (HeSSup) study’s follow-up questionnaire in 2012. The study is based on a random Finnish population sample. Satisfaction was studied based on the question “How satisfied are you with your local health care services?” Demographic factors, obesity, self-assessed health status, depressive mood (BDI-12 questionnaire), New York Heart Association class, and chronic diseases were asked in the questionnaire. Questions describing local health care services were also presented. We assessed the association of an assigned and named GP and the respondents’ proactivity in contacting the same doctor with satisfaction. We used crosstabulation and binary logistic regression in the analyses. Results The Health and Social Support study was answered in 2012 by 15,993 participants (45.4%) and majority (61.3%) was satisfied with their local health care services. An assigned and named GP (OR 1.79; 95% CI 1.67–1.92) and the respondent’s proactivity in contacting the same doctor (OR 1.23; 95% CI 1.15–1.32) were associated with satisfaction in the adjusted multivariate analysis. BDI score Conclusions A named GP in primary care proved to have a positive correlation with patient satisfaction. Depression was associated with decreased satisfaction. A named GP indicates continuity of care, and it should be seriously considered when planning treatment for patients with chronic conditions.

Summary Purpose Black Bone (BB) magnetic resonance imaging (MRI) is a nonionizing imaging method and a recent alternative to computed tomography (CT) in the examination of cranial deformities. The purpose of this study was to compare BB-MRI and routine 3D-CT in the preoperative evaluation of patients with craniosynostosis. Methods At our center, we have routinely performed preoperative CT of the skull and brain MRI for patients with clinical suspicion of craniosynostosis. We recently changed our MRI protocol into one that includes sequences for the evaluation of both brain anatomy and skull bone and sutures by BB-MRI. A semi-automatic skull segmentation algorithm was developed to facilitate visualization. Both BB-MRI and 3D-CT were performed on 9 patients with clinical craniosynostosis, and the images were evaluated by two craniofacial surgeons, one pediatric neurosurgeon, and two neuroradiologists. Results We obtained informative 3D images using BB-MRI. Six (6/9) patients had scaphocephaly, 1 (1/9) patient had unicoronal synostosis, and 2 (2/9) patients had lambdoid synostosis. The affected synostotic sutures could be identified both by BB-MRI and by 3D-CT in all patients. Intra-rater and inter-rater reliability for rating the calvarial sutures was high. However, the reliability for rating the intracranial impressions was low by both imaging methods. Conclusion BB-MRI is an alternative to 3D-CT in the preoperative evaluation of patients with craniosynostosis. BB-MRI provides information not only on cranial sutures and intracranial impressions but also on the brain structure in one imaging session. This method can replace ionizing radiation-based methods in analyzing skull deformities.

A method was developed for quantitative estimation of illicit psychostimulants in blood, with an emphasis on new psychoactive substances, based on gas chromatography nitrogen chemiluminescence detection coupled with atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (GC-NCD-APCI-QTOFMS). Quantitative estimation relied on the NCD’s N-equimolar response to nitrogen, using amphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and methylenedioxypyrovalerone as external calibrators for prim-, sec- and tert- amines, respectively. After spiking with 38 stimulants at 3 concentration levels, the donor blood samples were submitted to liquid–liquid extraction at a basic pH followed by acylation with trifluoroacetic anhydride. All but 3 psychostimulants could be analyzed with a limit of quantification (LOQ) of 0.05 mg/L. At LOQ, the coefficient of variation (CV) values for between-day accuracy was 62.3–143.3% (mean, 93.5%; median, 88.5%) and precision 6.6–22.4% (mean, 15.8%; median, 16.1%). In addition, 11 post-mortem blood samples, containing 0.08–2.4 mg/L of amphetamine (n = 5), methamphetamine (n = 4) or MDMA (n = 4), were analyzed by the GC-NCD-APCI-QTOFMS method, and the results were compared with an established electron ionization GC–MS method with appropriate calibration. The agreement between the 2 methods was 62.5–117.3%. Regarding identification, the APCI source permitted detection of the intact precursor ion, or the respective acylation product, for all of the measured compounds. The GC-NCD-APCI-QTOFMS method developed here enables instant quantitative estimation of illicit psychostimulants in blood at reasonable accuracy, without the necessity of possessing the true reference standards for each analyte.

Flualprazolam is a novel designer benzodiazepine, structurally related to alprazolam, flubromazolam and triazolam. In the last couple of years, it has been frequently detected in seizures and in forensic cases in Sweden and Finland. However, there is a lack of published blood concentrations for the drug, which presents difficulties when assessing its relevance for the cause of death. A quantitative method for the determination of flualprazolam in post-mortem blood was developed and validated, and subsequently used to analyse samples from 33 deaths previously screened as testing positive for flualprazolam in Sweden and Finland. Most of the cases in the study were accidental deaths (61 %) or suicides (18 %). The median (range) flualprazolam concentration was 18.0 (3.0-68) ng/g. The majority of the deceased were male (82 %) and the median age was 30 years. The median age in the Swedish cases was significantly higher (35 years) than in the Finnish cases (23 years) (p

Purity assessment of seized material containing new psychoactive substances (NPS) is complicated without appropriate primary reference standards. Here we present a method for fast quantitative estimation of stimulant-type NPS with use of secondary reference standards, based on gas chromatography nitrogen chemiluminescence detection coupled with atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (GC-NCD-APCI-QTOFMS). Quantification was based on the detector’s N-equimolar response to nitrogen and using two external nitrogen-containing calibrators, MDMA for prim- and sec- amines and α-PVP for tert- amines. Sample preparation involved dissolving the seized powdery material in an organic solvent mixture followed by acylation with N-methyl-bis-trifluoroacetamide (MBTFA). The method’s between-day accuracy and precision over a five-day period was measured for twenty-eight stimulants: the grand mean equimolarity was 91.9% (CV 5.5%), as compared with primary reference standards. The GC-NCD-APCI-QTOFMS method was applied to the purity estimation of forty-two seized powder samples previously found to contain stimulant-type NPS by appropriate methods. The quantitative results were compared to those obtained by an established method relying on liquid chromatography chemiluminescence detection (LC-CLND), the latter using caffeine as an external calibrator. The mean difference of purity values between the methods was 8.1% (range 0.4 - 26.7%). The presented method might find use as a tool for instant purity assessment in forensic laboratories.

Despite some promising results, the majority of patients do not benefit from T cell therapies, as tumors prevent T cells from entering the tumor, shut down their activity, or downregulate key antigens. Due to their nature and mechanism of action, oncolytic viruses have features that can help overcome many of the barriers currently facing T cell therapies of solid tumors. This study aims to understand how four different oncolytic viruses (adenovirus, vaccinia virus, herpes simplex virus, and reovirus) perform in that task. For that purpose, an immunocompetent in vivo tumor model featuring adoptive tumor-infiltrating lymphocyte (TIL) therapy was used. Tumor growth control (p < 0.001) and survival analyses suggest that adenovirus was most effective in enabling T cell therapy. The complete response rate was 62% for TILs + adenovirus versus 17.5% for TILs + PBS. Of note, TIL biodistribution did not explain efficacy differences between viruses. Instead, immunostimulatory shifts in the tumor microenvironment mirrored efficacy results. Overall, the use of oncolytic viruses can improve the utility of T cell therapies, and additional virus engineering by arming with transgenes can provide further antitumor effects. This phenomenon was seen when an unarmed oncolytic adenovirus was compared to Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (TILT-123). A clinical trial is ongoing, where patients receiving TIL treatment also receive TILT-123 (ClinicalTrials.gov: NCT04217473)., Graphical Abstract

We describe the sudden death of a middle-aged man while having a sauna under the influence of α-pyrrolidinovalerophenone (α-PVP) (PM blood concentration: 0.8 mg/L), amphetamine (0.34 mg/L), and other drugs (buprenorphine, benzodiazepines), and engaging in solitary sexual activities. The drugs’ effects on the cardio-circulatory system and on body thermoregulation combined with the high temperatures are likely to have been central mechanisms leading to death. The high levels of adrenaline triggered by sexual arousal and the respiratory depression caused by buprenorphine, in association with benzodiazepines, may have also contributed to his death. This previously unreported type of accidental autoerotic death illustrates the risk of using amphetamine-like sympathomimetic drugs (e.g. cathinone derivates) in hot environments such as a sauna, and during sexual activities therein.

Diabetes mellitus (DM) could cause pilot incapacitation and result in aviation fatalities. The mechanisms could be directly as a consequence of acute hypoglycemia/subacute diabetic ketoacidosis (DKA) or indirectly as an acute cardiovascular event by contributing to the development of atherosclerosis in coronary or carotid and cerebral arteries. In this study, DM-related fatal flight accidents in the US National Transport Bureau's database between years 2011-2016 were analyzed with special emphasis on postmortem (PM) glucose levels and correlation of toxicological reports with anamnestic information on DM. Additionally, autopsy results on coronary arteries were reviewed. In 43 out of 1491 (similar to 3%) fatal accidents pilots had DM. Postmortem glucose or glycated hemoglobin percentage (Hb1Ac) was measured in 12 of the 43 cases; while antidiabetic medication was found in 14 of the cases (only two of the cases had both glucose measurements and medication). With the increasing prevalence of DM, a possibility of pilot incapacitation due to DM or complications of DM should be actively studied, even if no anamnestic information of DM was available. While PM hypoglycemia is difficult to assess, we propose a systematic investigation based on measurement of glucose, Hb1Ac%, and ketone bodies, and documentation of atherosclerotic lesions in major arteries to identify or rule out DM as a cause of pilot incapacitation.

Autosomal DNA data from Peru for human identity testing purposes are scarce in the scientific literature, which hinders obtaining an appropriate portrait of the genetic variation of the resident populations. In this study we genetically characterize five populations from the Northeastern Peruvian Andes (Chachapoyas, Awajun, Wampis, Huancas and Cajamarca). Autosomal short tandem repeat (aSTR) and identity informative single nucleotide polymorphism (iiSNP) data from a total of 233 unrelated individuals are provided, and forensic genetic parameters are calculated for each population and for the combined set Northeastern Peruvian Andes. After correction for multiple testing in the whole dataset of the Northeastern Peruvian Andes, the only departure from Hardy-Weinberg equilibrium was observed in locus rs2111980. Twenty one out of 27 aSTR loci exhibited an increased number of alleles due to sequence variation in the repeat motif and flanking regions. For iiSNPs 33% of the loci displayed flanking region variation. The combined random match probability (RMP), assuming independence of all loci (aSTRs and iiSNPs), in the Chachapoyas, the population with the largest samples size (N = 172), was 8.14 x 10(-62) for length-based data while for sequence-based was 4.15 x 10(-67). In the merged dataset (Northeastern Peruvian Andes; N = 233), the combined RMP when including all markers were 2.96 x 10(-61) (length-based) and 3.21 x 10(-66) (sequence-based). These new data help to fill up some of the gaps in the genetic canvas of South America and provide essential length- and sequence-based background information for other forensic genetic studies in Peru.

It is not known how mortality differs between psychopathic and nonpsychopathic individuals. We linked data from subjects having been in forensic mental examinations at Niuvanniemi Hospital during 1984–1993 to the data from the National Death Registry to estimate the association between psychopathy and mortality. One hundred psychopathic individuals scoring 25 or higher in the PCL-R scale were followed up for 20–30 years. Two control groups were used as follows: 178 offenders scoring less than 25 on the PCL-R, and sample of general population drawn from the Finnish National Statistics database. Results reveal that psychopaths die younger than the general population, and the causes of death are more violent than in the nonpsychopath control group. There was a significant positive correlation between PCL-R score and mortality, and the mortality among psychopaths was about fivefold when compared with general population.

CYP2D6 is a key pharmacogene encoding an enzyme impacting poor, intermediate, extensive and ultrarapid phase I metabolism of many marketed drugs. The pharmacogenetics of opiate drug metabolism is particularly interesting due to the relatively high incidence of addiction and overdose. Recently, trans-acting opiate metabolism and analgesic response enzymes (UGT2B7, ABCB1, OPRM1 and COMT) have been incorporated into pharmacogenetic studies to generate more comprehensive metabolic profiles of patients. With use of massively parallel sequencing, it is possible to identify additional polymorphisms that fine tune, or redefine, previous pharmacogenetic findings, which typically rely on targeted approaches. The 1000 Genomes Project data were analyzed to describe population genetic variation and statistics for these five genes in self-reported healthy individuals in five global super- and 26 sub-populations. Findings on the variation of these genes in various populations expand baseline understanding of pharmacogenetically relevant polymorphisms for future studies of affected cohorts.

U-47,700 is a synthetic opioid that emerged on the novel psychoactive substance market a few years ago. After incorporating the substance into the urine UPLC-TOF-MS screening used in post-mortem toxicology, the drug was detected in 10 autopsy cases within routine case work. In all cases, the cause of death was accidental poisoning by U-47,700 alone or in combination with other psychoactive substances. The concentration of U-47,700 in the blood samples ranged between 0.15-2.0 mg/L with a median of 0.30 mg/L. In one of the cases with a U-47,700 concentration of 0.27 mg/L, no other psychoactive substances were detected. The stored TOF-MS analytical data from the year preceding the incorporation of U-47,700 into the screening was reprocessed in order to search for more positive cases. The data-independent acquisition of the original screening allowed for retrospective re-analysis of the full-scan data without additional experiments on the actual sample. The retrospective data-analysis revealed two additional cases positive for U-47,700. The first mention of U-47,700 on a Finnish internet discussion forum was in March 2015. After having been detected in several death cases, the drug was put under national control in November 2016 and the last fatality occurred in 2017. The toxic lifespan of U-47,700 thus lasted for approximately 2 years in Finland. Forensic and clinical laboratories need to rapidly adjust their screening procedures in order to adapt to the continuously expanding field of novel psychoactive substances. Retrospective data-analysis is a practical tool for monitoring the emergence of new substances onto the market. (C) 2019 Elsevier B.V. All rights reserved.

Non

Estimation of an individual’s age has important applications in forensics. In young individuals, it often relies on separate evaluations of permanent teeth (PT) and third molars (TM) development. Here we analysed the age prediction performance of combined information from PT and TM in an unusual sample of healthy Somalis, born and living in Finland. PT development was staged according to Demirjian et al. (Hum Biol, 1973) and TM development according to Köhler et al. (Ann Anat, 1994), using panoramic radiographs from 803 subjects (397 males, 406 females) aged 3-23 years. A sex-specific Bayesian age-estimation model for the multivariate distribution of the stages conditional on age was fitted on PT, TM, and PT and TM combined. The age-estimation performances were validated and quantified. The approach combining PT and TM only overestimated age with an ME of -0.031 years in males and -0.011 years in females, indicating the best age prediction performance. ispartof: INTERNATIONAL JOURNAL OF LEGAL MEDICINE vol:133 issue:4 pages:1207-1215 ispartof: location:Germany status: Published online

AIM: The aim of the current study was to retrospectively collect dental panoramic radiographs from Somali children living in Finland, to use the radiographic data to develop a new age estimation model based on the model established by Willems et al. (J Forensic Sci 46(4):893-895, 2001), and to compare the age prediction performances of the Willems et al. model (WM) and the newly developed model. MATERIAL AND METHODS: Dental panoramic radiographs from 808 healthy Somalis born in Finland were selected. The development of the seven left mandibular permanent teeth, from the central incisor to the second molar, was staged according to Demirjian et al. (Hum Biol 45(2):211-227, 1973). Radiographs with all listed permanent teeth completely developed were excluded. The studied sample consisted of 635 subjects (311 females, 324 males) ranging in age from 4 to 18 years. Kappa and weighted Kappa statistics were used to quantify intra- and inter-observer agreement in stage allocation. The collected dataset was used to validate the WM, constructed on a Belgian Caucasian reference sample, and to establish a Somali-specific age estimation model (SM) based on the WM. Both models were validated and their age prediction performances quantified using mean error (ME), mean absolute error (MAE) and root mean squared error (RMSE). RESULTS: The SM resulted in a slight underestimation of age when the sex groups were analysed separately or combined, with ME varying between 0.04 (standard deviation (SD) 1.01) and 0.05 (SD 1.04) years, MAE between 0.77 and 0.80 years and RMSE between 1.01 and 1.04 years. The WM statistically significantly underestimated the age of females, with an ME of 0.20 (SD 1.01) years (p = 0.0006). For males, and for females and males combined, no statistically significant ME was observed. CONCLUSION: The WM and SM were similar in their age prediction performances, and the use of the WM in dental age assessment in the Somali population is justified. ispartof: INTERNATIONAL JOURNAL OF LEGAL MEDICINE vol:132 issue:6 pages:1-8 ispartof: location:Germany status: published

Many native populations in South America have been severely impacted by two relatively recent historical events, the Inca and the Spanish conquest. However decisive these disruptive events may have been, the populations and their gene pools have been shaped markedly also by the history prior to the conquests. This study focuses mainly on the Chachapoya peoples that inhabit the montane forests on the eastern slopes of the northern Peruvian Andes, but also includes three distinct neighboring populations (the Jívaro, the Huancas and the Cajamarca). By assessing mitochondrial, Y-chromosomal and autosomal diversity in the region, we explore questions that have emerged from archaeological and historical studies of the regional culture (s). These studies have shown, among others, that Chachapoyas was a crossroads for Coast-Andes-Amazon interactions since very early times. In this study, we examine the following questions: 1) was there pre-Hispanic genetic population substructure in the Chachapoyas sample? 2) did the Spanish conquest cause a more severe population decline on Chachapoyan males than on females? 3) can we detect different patterns of European gene flow in the Chachapoyas region? and, 4) did the demographic history in the Chachapoyas resemble the one from the Andean area? Despite cultural differences within the Chachapoyas region as shown by archaeological and ethnohistorical research, genetic markers show no significant evidence for past or current population substructure, although an Amazonian gene flow dynamic in the northern part of this territory is suggested. The data also indicates a bottleneck c. 25 generations ago that was more severe among males than females, as well as divergent population histories for populations in the Andean and Amazonian regions. In line with previous studies, we observe high genetic diversity in the Chachapoyas, despite the documented dramatic population declines. The diverse topography and great biodiversity of the northeastern Peruvian montane forests are potential contributing agents in shaping and maintaining the high genetic diversity in the Chachapoyas region.

Various psychiatric problems in adolescence and early adulthood have been shown to associate with criminal behaviour. In this study the association of personality disorders (PDs) with criminal behaviour was examined in adolescents treated in psychiatric hospitals. The study sample consisted of 508 adolescents (age 13-17) admitted to acute psychiatric impatient care between April 2001 and March 2006. Crime data was obtained from the Finnish Legal Register Centre on September 2013. The Schedule for Affective Disorder and Schizophrenia for School-Age Children Present and Lifetime (K-SADS-PL) was used to assess psychiatric diagnoses in adolescence. The information on PDs in early adulthood was based on follow-up information on psychiatric treatments in either out-or inpatient settings until the end of 2012, and was extracted from the National Care Register for Health Care provided by the Finnish National Institute for Health and Welfare. A total of 22 (39%) of the 57 subjects with PD had committed a crime. In women, the likelihood for violent criminality was significantly increased in those with Borderline PD (OR 6.09, CI 1.24-29.84, p = 0.009) and was also associated with conduct disorder (OR 4.26, CI 1.38-13.19, p = 0.012), child welfare placement (OR 11.82, CI 3.61-38.76, p

We reviewed the 33 727 postmortem toxicology investigations performed in Finland over a period of 5 years (2009-2013) and identified those in which the antidepressant bupropion was detected. Cases positive for other antidepressant drugs were reviewed for comparison. The postmortem toxicological examination included, in all cases, the routine screening and quantification of hundreds of drugs and poisons using quality-controlled methods. Bupropion was detected in 65 cases. A large proportion of the bupropion-positive deaths resulted from suicide (55%). In fatal poisoning cases found positive for bupropion, the proportion of suicide was even higher (77%). The measured median bupropion postmortem blood concentration (0.69 mg/L) was markedly higher than the normal therapeutic range in plasma in the treatment of depression (up to 0.1 mg/L) and even higher in fatal bupropion poisonings (13 mg/L). Only 14% of the deceased positive for bupropion were estimated to be drug abusers. However, nearly all of the drug abuse cases were from the last year of the study (2013), indicating a recent increase of the use of bupropion among drug abusers and possibly even abuse of bupropion itself. Suicide victims positive for bupropion were younger than those who died with other antidepressant drugs in their blood. In addition, the percentage of fatal poisonings among bupropion-positive postmortem cases was higher than among the users of other antidepressant drugs. Suicide was significantly more common among the deceased positive for bupropion than among users of other antidepressant drugs. An unknown degree of bupropion degradation before the assay and post-mortem redistribution of bupropion may have impacted the measured levels. Nonetheless, all post-mortem concentrations of bupropion were elevated and especially high concentrations were detected in suicides. (C) 2016 Elsevier Ireland Ltd. All rights reserved.