Sex estimation from coxal bones using deep learning in a population balanced by sex and age.

In the field of forensic anthropology, researchers aim to identify anonymous human remains and determine the cause and circumstances of death from skeletonized human remains. Sex determination is a fundamental step of this procedure because it influences the estimation of other traits, such as age and stature. Pelvic bones are especially dimorphic, and are thus the most useful bones for sex identification. Sex estimation methods are usually based on morphologic traits, measurements, or landmarks on the bones. However, these methods are time-consuming and can be subject to inter- or intra-observer bias. Sex determination can be done using dry bones or CT scans. Recently, artificial neural networks (ANN) have attracted attention in forensic anthropology. Here we tested a fully automated and data-driven machine learning method for sex estimation using CT-scan reconstructions of coxal bones. We studied 580 CT scans of living individuals. Sex was predicted by two networks trained on an independent sample: a disentangled variational auto-encoder (DVAE) alone, and the same DVAE associated with another classifier (Crecon). The DVAE alone exhibited an accuracy of 97.9%, and the DVAE + Crecon showed an accuracy of 99.8%. Sensibility and precision were also high for both sexes. These results are better than those reported from previous studies. These data-driven algorithms are easy to implement, since the pre-processing step is also entirely automatic. Fully automated methods save time, as it only takes a few minutes to pre-process the images and predict sex, and does not require strong experience in forensic anthropology.

Alpha-methyltryptamine and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) fatal co-intoxication: case report and review of literature.

The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

A non-randomized pilot trial of the use of prazosin in the prevention of transition from acute stress disorder to post-traumatic stress disorder.

BACKGROUND: Following a traumatic event, 40-80% of the patients with acute stress disorder (ASD) will develop post-traumatic stress disorder (PTSD), 67% at 6 months. Alpha1-blockers are effective in treating some symptoms of PTSD but their usefulness in acute stress situations remains unclear. We hypothesized that reducing noradrenergic hyperactivity with an alpha1-blocker during the acute phase after a traumatic event could prevent the transition to PTSD in patients with ASD. OBJECTIVE: To investigate the efficacy and safety of a 1-month course of alpha1-blocker (prazosin) to prevent the transition to PTSD in patients with ASD at 6 months. METHOD: In a monocentric open-label prospective pilot study, 15 patients with ASD were included within 3-7 days of exposure to a traumatic event. After enrolment, they received prazosin LP at home at bedtime at 2.5 mg/day for 7 days and then 5 mg/day for 21 days. Incidence of PTSD was assessed at 6 months using the Clinician Administrated PTSD Scale (CAPS). RESULTS: At 6 months, 22% of patients who completed the study (2/9) met the diagnostic criteria for PTSD. This rate was significantly lower than that observed in previous studies (67%; p = .047). The treatment was well tolerated and there were no serious adverse events. CONCLUSIONS: These preliminary findings indicating the safety of prazosin and suggesting its potential to prevent the development of PTSD in ASD require to be replicated in large-scale randomized placebo-controlled studies.Trial registration: The study was pre-registered on a public database (www.clinicalTrials.gov identifier: NCT03045016).

Alpha1-blockers are safe and well tolerated in patients with acute stress disorder.The use of alpha1-blockers 3­7 days after traumatic exposure is worthy of study.Alpha1-blockers could prevent the transition to PTSD in ASD patients at 6 months.

α-Methyltryptamine (α-MT) Metabolite Profiling in Human Hepatocyte Incubations and Postmortem Urine and Blood.

α-MT is a hallucinogenic and stimulant tryptamine that was involved in several overdose fatalities in the United States and Europe. Analytical toxicology, and particularly the identification of metabolite biomarkers in biological samples, often is the only way to prove tryptamine use in clinical and forensic caseworks. We aimed to identify optimal α-MT metabolite biomarkers of consumption in humans. We identified α-MT metabolites in 10-donor-pooled human hepatocyte incubations and postmortem urine and blood from an α-MT overdose case using in silico metabolite predictions, liquid chromatography high-resolution-tandem mass spectrometry (LC-HRMS/MS), and software-assisted data mining. Nine metabolites were identified in vitro and eight additional metabolites were found in urine; five metabolites were found in blood. Metabolic transformations were hydroxylation, O-sulfation, O-glucuronidation, N-glucuronidation, and N-acetylation, consistent with the metabolism of structural analogues. The findings in hepatocyte incubations and postmortem samples were consistent, proving the in vitro model suitability. We suggest α-MT, hydroxy-α-MT glucuronide, and two hydroxy-α-MT sulfates as biomarkers of α-MT use in non-hydrolyzed urine; we suggest α-MT, two hydroxy-α-MT sulfates and N-acetyl-α-MT as biomarkers of α-MT use in blood. Further studies on α-MT clinical and forensic caseworks with different doses and routes of administration are necessary to better explore α-MT metabolism.

Non-accidental head injury of infants: legal implications for the pediatric neurosurgeon.

BACKGROUND: Though the neurosurgeon's role in non-accidental head injury (NAHT) is the prompt recognition and care of the inflicted injuries, he/she should be aware of the possible legal implications related to this particular neurosurgical condition. MATERIAL AND METHODS: Based on published data and their own clinical and medico-legal practice, the authors review the role of the neurosurgeon in NHAT. RESULTS: Besides the contribution that can be given by the neurosurgeon to a correct differential diagnosis, he/she is likely to be involved in the interpretations of the pathological findings in the case where the judge may request for a medical opinion concerning etiology, circumstances, severity, and consequences. As a member of a multidisciplinary team, usually the neurosurgeon is only requested for information regarding the lesions he was called to recognize and treat. Nevertheless, such information may have a pivotal part in the evaluation process. Consequently, the neurosurgeon should be able to reach a correct differential diagnosis of NAHT among all the events that may share similar clinical and anatomo-pathological characteristics and be aware of the ongoing scientific controversies related to the diagnosis and pathophysiology. CONCLUSIONS: In practical terms, the pediatric neurosurgeon is called to individuate and record all the precise details of the condition to be eventually offered to the judge in case of controversy. Whereas the diagnosis of NAHT should be evoked at the initial phase in order not to leave the child unprotected, all possible alternative hypotheses should be ruled out "beyond reasonable doubt" for the court. The medical file should be maintained in the record carefully and be accessible even after a long time.

Toxicological detection of pholcodine in blood, urine and hair in three cases of fatal intoxication.

Pholcodine is an opioid antitussive reputed for its low toxicity and absence of addictive effect. We report three cases of pholcodine intoxication with fatal outcome. Large concentrations of pholcodine were quantified by gas chromatography coupled to mass spectrometry (GC/MS) in peripheral postmortem blood (respectively 2890 ng/mL, 979 ng/mL and 12,280 ng/mL). Segmental hair analyses by GC/MS and detected pholcodine in three 1.5-2 cm segments (38-161 ng/mg, 8.54-41.6 ng/mg, and 0.26-2.66 ng/mg, respectively). These findings underline that pholcodine can be involved in fatal poisoning and raise the question of misuse or abuse and of taking account of this drug in opioid overdose prevention policies.

Detection of insulins in postmortem tissues: an optimized workflow based on immunopurification and LC-MS/HRMS detection.

Diabetes is a worldwide disease in perpetual expansion. Type 1 and sometimes type 2 diabetic patients require daily human insulin (HI) or analog administration. Easy access to insulins for insulin-treated diabetics, their relatives, and medical professionals can enable abuse for suicidal or homicidal purpose. However, demonstrating insulin overdose in postmortem blood is challenging. Tissue analyses are contributive, as insulins can accumulate before death or undergo only limited degradation. The present study describes an assay for HI and synthetic analogs (lispro, aspart, glulisine, detemir and degludec, glargine and its main metabolite (M1)) in liver, kidney, muscle, and injection site samples. It is based on a 5-step sample preparation (reduction of tissue sample size, homogenization, extraction, concentration, and immunopurification) associated with liquid chromatography coupled to high-resolution mass spectrometry (LC-MS/HRMS). Selectivity and limit of detection (LOD) for all target analogs were assessed in the above matrices. LOD was determined at 25 ng/g for HI and for analogs except detemir and degludec, where LOD was 50 ng/g in kidney and injection site samples and 80 ng/g in the liver and muscle. The method was applied to13 forensic cases in which insulin use was suspected.

False Rape Allegation and Regret: A Theoretical Model Based on Cognitive Dissonance.

The aim of this paper is to provide a model illustrating how regretful consensual intercourse may lead to false rape allegations (FRA). An intrapersonal perspective of regret based on cognitive dissonance is added to the interpersonal factors already mentioned in the literature. The intrapersonal perspective is discussed in terms of the reduction of a state of cognitive dissonance induced by the gap between social norms and the shamefully perceived behavior. First, we start with the review of the different motives that may lead to a FRA, insisting on regret caused by cognitive dissonance. We then develop the emergence of regret from a state of cognitive dissonance. Second, we describe the means used to build the model: a literature review, an extraction of the factors at play in regret-based FRA, a chronological structure of the various factors, as some are necessarily the source of others. We then build the model. Third, we illustrate how the model could encompass many possible and usual scenarios. Thirteen plausible scenarios were developed to show the relevance of the model. Finally, we comment and discuss the model for future research and prevention.

Fatal intoxication involving 4-methylpentedrone (4-MPD) in a context of chemsex.

4-methylpentedrone (4-MPD) is a new psychoactive substance (NPS) belonging to the cathinone class. We report an original case of death mainly involving 4-MPD, along with cocaine, sildenafil, bromazepam and nevirapine. The investigation data and the autopsy findings indicated fatal intoxication in a chemsex context (drug use during sex). 4-MPD concentrations were determined in peripheral blood (1285 ng/mL), cardiac blood (1128 ng/mL), urine (>10,000 ng/mL), bile (1187 ng/mL) and vitreous humor (734 and 875 ng/mL in left and right samples, respectively) by gas chromatography (GC) coupled to tandem mass spectrometry. 4-MPD metabolites were explored by GC coupled to high resolution mass spectrometry. Due to the paucity of data concerning 4-MPD, its use and effects were gathered from online user testimonies. This case illustrates the toxicity of this infrequent pentedrone derivate and confirms the significant overdose risk associated with chemsex.

Forensic autopsy-confirmed COVID-19-induced out-of-hospital cardiac arrest.

BACKGROUND: In the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, data from autopsy in subjects who died at home during lockdown are scarce. We here report the first forensic autopsy series of coronavirus disease 2019 (COVID-19)-related out-of-hospital cardiac arrest (OHCA). METHODS: Between March and April 2020, four COVID-19-related OHCA were autopsied at the Institute of Legal Medicine of the metropolitan area of Lyon (France) according safe recommended procedures. RESULTS: Four Caucasian individuals (3 men/1 woman; age: 56.8±2.1 years, body mass index: 29.5±7.4 kg/m2), presenting symptomatic COVID-19 were autopsied. Autopsies of 3 individuals reported natural death by acute respiratory failure implicating SARS-CoV-2 with typical COVID-19 pulmonary aspect of gross findings and pulmonary microscopy findings, i.e., diffusely congestive edematous lungs with peripheral thrombi and diffuse alveolar damage (DAD) at different stages of inflammatory reaction. For one individual, autopsy concluded of violent death due to suicidal acute alcohol intoxication in a patient that could no longer endure COVID-19 lockdown. No significant lesions were found in the heart. CONCLUSIONS: We report here OHCAs of non-cardiac cause directly implicating COVID-19 at various stages of SARS-CoV-2-related DAD. Thus, autopsy remain of interest during this epidemic, both legally and medically to better understand the pathogenic processes of this emerging infectious disease.

Fatal 4-MEC Intoxication: Case Report and Review of Literature.

ABSTRACT: Synthetic cathinones are one of the major pharmacological families of new psychoactive substances and 4-methylethcathinone (4-MEC) has emerged in recent years as a recreational psychostimulant. We report a case of a 35-year-old man found dead and naked at home by his friend. Although no anatomic cause of death was observed at autopsy, toxicological analysis identified 4-MEC and hydroxyzine at therapeutic level (160 ng/mL). 4-Methylethcathinone was quantified in autopsy samples by a validated method consisting in liquid-liquid extraction and gas chromatography coupled to tandem mass spectrometry: peripheral blood, 14.6 µg/mL; cardiac blood, 43.4 µg/mL; urine, 619 µg/mL; vitreous humor, right 2.9 µg/mL and left 4.4 µg/mL; bile, 43.5 µg/mL; and gastric content, 28.2 µg/mL. The cause of death was 4-MEC intoxication and the manner of death could be either accidental or suicidal. The literature concerning 4-MEC was reviewed, focusing on distribution in classical postmortem matrices and 4-MEC metabolism and postmortem redistribution and stability.

Is insulin intoxication still the perfect crime? Analysis and interpretation of postmortem insulin: review and perspectives in forensic toxicology.

Insulin is an anabolic hormone essential to glucose homeostasis. Insulin therapy, comprising human insulin (HI) or biosynthetic analogs, is critical for the management of type-1 diabetes and many of type-2 diabetes. However, medication error including non-adapted dose and confusion of insulin type, and misuse, such as massive self-administration or with criminal intent, can have lethal consequences. The aim of this paper is to review the state of knowledge of insulin analysis in biological samples and of the interpretation of insulin concentrations in the situation of insulin-related death investigations. Analytic aspects are considered, as quantification can be strongly impacted by methodology. Immunoanalysis, the historical technique, has a prominent role due to its sensitivity and ease of implementation. Recently, liquid chromatography coupled to mass spectrometry has provided indispensable selectivity in forensic contexts, distinguishing HI, analogs, and degradation products. We review the numerous antemortem (dose, associated pathology, injection-to-death interval, etc.) and postmortem parameters (in corpore degradation, in vitro degradation related to hemolysis, etc.) involved in the interpretation of insulin concentration. The interest and limitations of various alternative matrices providing a valuable complement to blood analysis are discussed. Vitreous humor is one of the most interesting, but the low diffusion of insulin in this matrix entails very low concentrations. Injection site analysis is relevant for identifying which type of insulin was administered. Muscle and renal cortex are matrices of particular interest, although additional studies are required. A table containing most case reports of fatal insulin poisoning published, with analytical data, completes this review. A logic diagram is proposed to highlight analytical issues and the main parameters to be considered for the interpretation of blood concentrations. Finally, it remains a challenge to provide reliable biological data and solid interpretation in the context of death related to insulin overdose. However, the progress of analytical tools is making the "perfect crime" ever more difficult to commit.

The prospects for application of computational anatomy in forensic anthropology for sex determination.

The purpose of this study is to assess the relevance of computational anatomy for the sex determination in forensic anthropology. A novel groupwise registration algorithm is used, based on keypoint extraction, able to register several hundred full body images in a common space. Experiments were conducted on 83 CT scanners of living individuals from the public VISCERAL database. In our experiments, we first verified that the well-known criteria for sex discrimination on the hip-bone were well preserved in mean images. In a second experiment, we have tested semi-automatic positioning of anatomical landmarks to measure the relevance of groupwise registration for future research. We applied the Probabilistic Sex Diagnosis tool on the predicted landmarks. This resulted in 62% of correct sex determinations, 37% of undetermined cases, and 1% of errors. The main limiting factors are the population sample size and the lack of precision for the initial manual positioning of the landmarks in the mean image. We also give insights on future works for robust and fully automatic sex determination.

Unpredictable Behavior Under the Influence of "Magic Mushrooms": A Case Report and Review of the Literature.

Fatalities implicating psychedelic mushrooms are not a common clinical situation in everyday forensic medicine. Despite classification as an illegal drug in many countries, psilocybin mushrooms have the reputation of being safe. We report the case of a young man who jumped from a second story balcony under the influence of psilocybin mushrooms. The psilocin assay was performed by gas chromatography coupled to an electron-impact ionization time-of-flight detector (GC-EI-TOF) after solid-phase extraction. Total psilocin was quantified in peripheral and cardiac blood as 60 and 67 ng/mL, respectively, and in urine (2230 ng/mL), bile (3102 ng/mL), and vitreous humor (57 ng/mL). This case report and review of literature highlights the danger of psilocybin mushrooms. Isolated use of psilocybin mushrooms by a regular consumer without psychiatric history, even under "safe" circumstances, can lead to a fatal outcome.

Third molar maturity index for indicating the legal adult age in southeastern France.

The estimation of age in living subjects is today a significant issue because of the increase in the situations in which it arises and its legal consequences. In line with the Study Group on Forensic Age Diagnostics of the German Association of Legal Medicine's recommendations, it is based on the concomitant use of physical examination and methods for estimating bone age and dental age. Given the variations between the populations, the use of the latter requires their validation on all the ethnic groups on which they can be used. This aim of this study was to access the interest of the Cameriere's third molar maturity index (I3M) to indicate if an individual had reached the age of 18 in a sample of individuals from southeastern France. The studied sample consisted of OPTs 339 (184 females and 155 males) subjects aged between 14 and 22 years old. A logistic regression analysis with the adult age and minor age as dichotomous dependent variable and gender and I3M as predictor variables showed that gender was not statistically significant in discriminating adults and minors. The receiver operating curve (ROC) analysis showed the best discrimination performance of the specific cut-off value of I3M<0.08 in discriminating adults from minors. The proportion of accurate classification was 0.897 and 0.916 for females and males, respectively. The specificity (Sp) and sensitivity (Se) results for females were 0.962 and 0.813, respectively. Sp and Se for males were 0.953 and 0.871, respectively. The Bayes post-test probability was 0.961 and 0.955 in females and males respectively. Obtained results showed that a cut-off value of I3M<0.08 may be an additional tool for indicating adult age in the tested population.

Histological dating of subdural hematoma in infants.

BACKGROUND: After infant deaths due to non-accidental head injury (NAHI) with subdural hematoma (SDH), the magistrates ask experts to date the traumatic event. To do so, the expert only has tools based on adult series of NAHI. We aimed to develop an SDH dating system applicable to infants aged under 3 years. METHODS AND RESULTS: We studied a retrospective multicenter collection of 235 infants who died between the ages of 0 and 36 months, diagnosed with SDH by forensic pathological examination and with known posttraumatic interval (PTI). Two pathologists assessed blindly and independently 12 histomorphological criteria relating to the clot and 14 relating to the dura mater in 73 victims (31 girls, 42 boys) whose median age was 3.8 months. Histopathological changes were significantly correlated with PTI for the appearance of red blood cells (RBCs) and the presence or absence of siderophages, and regarding the dura mater, the quantity of lymphocytes, macrophages, and siderophages; presence or absence of hematoidin deposits; collagen and fibroblast formation; neomembrane thickness; and presence or absence of neovascularization. Dating systems for SDH in adults are not applicable to infants. Notably, neomembrane of organized connective tissue is formed earlier in infants than in adults. CONCLUSION: Our dating system improves the precision and reliability of forensic pathological expert examination of NAHI, particularly for age estimation of SDH in infants. However, the expert can only define a time interval. Histopathology is indispensable to detect repetitive trauma.

Quantitative comparison of human myocardial fiber orientations derived from DTI and polarized light imaging.

Diffusion tensor imaging (DTI) is a non-invasive technique used to obtain the 3D fiber structure of whole human hearts, for both in vivo and ex vivo cases. However, by essence, DTI does not measure directly the orientations of myocardial fibers. In contrast, polarized light imaging (PLI) allows for physical measurements of fiber orientations, but only for ex vivo case. This work aims at quantitatively comparing the myocardial fiber orientations of whole human hearts obtained from cardiac DTI with those measured by PLI. Whole human neonatal and infant hearts were first imaged using DTI. The same whole hearts were then imaged using PLI. After DTI and PLI data are registered, the orientations of fibers from the two imaging modalities were finally quantitatively compared. The results show that DTI and PLI have similar variation patterns of elevation and azimuth angles, with some differences in transmural elevation angle range. DTI itself induces an underestimation of the range of transmural elevation angles by a factor of about 25° at the basal and equatorial slices and the reduction of spatial resolution further decreases this range. PLI data exhibit a 15° ± 5° (P < 0.01) narrower transmural elevation angle range at apical slices than in basal or equatorial slices. This phenomenon is not observed in DTI data. In both modalities, the azimuth angle maps exhibit curved or twisting boundaries at the basal and apical slices. The experimental results globally enforce DTI as a valid imaging technique to reasonably characterize fiber orientations of the human heart noninvasively.

Extraction of the 3D local orientation of myocytes in human cardiac tissue using X-ray phase-contrast micro-tomography and multi-scale analysis.

This paper presents a methodology to access the 3D local myocyte arrangements in fresh human post-mortem heart samples. We investigated the cardiac micro-structure at a high and isotropic resolution of 3.5 µm in three dimensions using X-ray phase micro-tomography at the European Synchrotron Radiation Facility. We then processed the reconstructed volumes to extract the 3D local orientation of the myocytes using a multi-scale approach with no segmentation. We created a simplified 3D model of tissue sample made of simulated myocytes with known size and orientations, to evaluate our orientation extraction method. Afterwards, we applied it to 2D histological cuts and to eight 3D left ventricular (LV) cardiac tissue samples. Then, the variation of the helix angles, from the endocardium to the epicardium, was computed at several spatial resolutions ranging from 3.63 mm3 to 1123 µm3. We measure an increased range of 20° to 30° from the coarsest resolution level to the finest level in the experimental samples. This result is in line with the higher values measured from histology. The displayed tractography demonstrates a rather smooth evolution of the transmural helix angle in six LV samples and a sudden discontinuity of the helix angle in two septum samples. These measurements bring a new vision of the human heart architecture from macro- to micro-scale.

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review.

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

Determination of Human Chorionic Gonadotropin in Postmortem Samples in Ectopic Pregnancies.

Increased human chorionic gonadotropin levels (HCG) can be detected in femoral blood, bile, and vitreous humor collected during autopsy of pregnant women using a standard kit designed for living patients. In the study herein, the concentrations of HCG were measured in postmortem serum, vitreous, bile, cerebrospinal, and pericardial fluids in 4 cases of fatal ectopic pregnancy and 40 controls using a quantitative electrochemiluminescence immunoassay designed for living patients. No false-negative cases were identified in any of the analyzed samples in any of the ectopic pregnancy cases. No correlations were found between total HCG levels in postmortem serum and the other tested specimens. The results of this study would suggest that higher HCG in bile, vitreous, pericardial, and cerebrospinal fluids may confirm the existence of ectopic pregnancy and therefore identify other situations in which this hormone is increased, although gestational age cannot be reliably estimated using these values.