Evidence for putative pathophysiological mechanisms of autism spectrum disorder (ASD), including peripheral inflammation, blood–brain barrier disruption, white matter alterations, and abnormal synaptic overgrowth, indicate a possible involvement of neuroinflammation in the disorder. Neuroinflammation plays a role in the development and maintenance of the dendritic spines involved in glutamatergic and GABAergic neurotransmission, and also influences blood–brain permeability. Cytokines released from microglia can impact the length, location or organization of dendritic spines on excitatory and inhibitory cells as well as recruit and impact glial cell function around the neurons. In this study, gene expression levels of anti- and pro-inflammatory signaling molecules, as well as oligodendrocyte and astrocyte marker proteins, were measured in both gray and white matter tissue in the anterior cingulate cortex from ASD and age-matched typically developing (TD) control brain donors, ranging from ages 4 to 37 years. Expression levels of the pro-inflammatory gene, HLA-DR, were significantly reduced in gray matter and expression levels of the anti-inflammatory gene MRC1 were significantly elevated in white matter from ASD donors as compared to TD donors, but neither retained statistical significance after correction for multiple comparisons. Modest trends toward differences in expression levels were also observed for the pro-inflammatory (CD68, IL1β) and anti-inflammatory genes (IGF1, IGF1R) comparing ASD donors to TD donors. The direction of gene expression changes comparing ASD to TD donors did not reveal consistent findings implicating an elevated pro- or anti-inflammatory state in ASD. However, altered expression of pro- and anti-inflammatory gene expression indicates some involvement of neuroinflammation in ASD. Lay Summary: The anterior cingulate cortex is an integral brain region in modulating social behaviors including nonverbal communication. The study found that inflammatory gene expression levels were altered in this brain region. We hypothesize that the inflammatory changes in this area could impact neuronal function. The finding has future implications in using these molecular markers to identify potential environmental exposures and distinct cell differences in autism.

Gray matter (GM) forms the ‘computational engine’ of our brain and plays the key role in brain function. Measures derived from MRI (e.g., structural MRI (sMRI) and diffusion MRI (dMRI)) provide a unique opportunity to non-invasively study GM structure in-vivo and thus can be used to probe GM pathology in development, aging and neuropsychiatric disorders. Investigation of the influence of various factors on MRI measures in GM is critical to facilitate their use for future non-invasive studies in healthy and diseased populations. In this dissertation, GM structure was studied with MRI to understand how it is influenced by genetic and environmental factors. Validation of dMRI- derived measures was conducted by comparing them with histological data from monkeys to better understand the cytoarchitectural features that influence GM measures. First, the influence of genetic and environmental factors was quantified on gray matter macrostructure and microstructure measures using phenotypic modelling of structural and diffusion MRI data obtained from a large twin and sibling population (N = 840). Results of this study showed that in GM, while sMRI measures like cortical thickness and GM volume are mainly affected by genetic factors, advanced dMRI measures of mean squared displacement (MSD) and return to origin probability (RTOP) derived from advanced biexponential model can tap into regionally specific patterns of both genetic and environmental influence in cortical and subcortical GM. Our results thus highlight the potential of these advanced dMRI measures for use in future studies that aim to investigate and follow in healthy and clinical population changes in GM microstructure linked with both genes and environment. Second, using data from a large healthy population (n=550), we investigated changes in sMRI tissue contrast at the gray-white matter boundary with biological development during adolescence to assess how this affects estimation of the developmental trajectory of cortical thickness. Results of this study suggest that increased myelination during brain development contributes to age-related changes in gray-white boundary contrast in sMRI scans causing an apparent shift of the estimated gray-white boundary towards the cortical surface, in turn reducing estimations of cortical thickness and its developmental trajectory. Based on these results, we emphasize the importance of accounting for the effects of myelination on T1 gray-white matter boundary contrast to enable more precise estimation of cortical thickness during neurodevelopment. Finally, we conducted histological validation of dMRI measures in gray matter by comparing dMRI measures derived from two models, conventional Diffusion Tensor Imaging (DTI) model and an advanced biexponential model with histology acquired from the same 4 rhesus monkeys. Results demonstrate differences in the ability of distinct dMRI measures including DTI-derived measures of fractional anisotropy (FA), Trace and advanced Biexponential model-derived measures of MSD and RTOP to capture the biological features of underlying cytoarchitecture and identify the dMRI measures that best reflect underlying gray matter cytoarchitectural properties. Investigation of the contribution of underlying cytoarchitecture (cellular organization) to dMRI measures in gray matter provides validation of dMRI measures of average and regional heterogeneity in MSD & Trace as markers of cytoarchitecture as measured by regional average and heterogeneity in cell area density. This postmortem validation of these dMRI measures makes their use possible for treatment monitoring of various GM pathologies. These studies and their results together demonstrate the utility of imaging measures to investigate the complex relationships between GM cellular organization, brain development, environment and genes.

Two deaths involving 3, 4-methylenedioxypyrovalerone (MDPV) are reported. MDPV is a synthetic cathinone stimulant found in "bath salts" with neurological and cardiovascular toxicity. Biological specimens were analyzed for MDPV by GC/MS and LC/MS. A White man was found dead with signs of nausea and vomiting after repeatedly abusing bath salts during a weekend binge. Femoral venous blood and urine had MDPV concentrations of 39 ng/mL and 760 ng/mL. The second fatality was a White man with a history of drug and bath salt abuse found dead at a scene in total disarray after exhibiting fits of anger and psychotic behavior. Femoral venous blood and urine had MDPV concentrations of 130 ng/mL and 3800 ng/mL. The blood and urine MDPV concentrations are within the reported recreational concentration ranges (blood 24-241 ng/mL and urine 34-3900 ng/mL). Both decedents' deaths were attributed to relevant natural causes in a setting of MDPV abuse.

Two deaths involving 3, 4-methylenedioxypyrovalerone (MDPV) are reported. MDPV is a synthetic cathinone stimulant found in "bath salts" with neurological and cardiovascular toxicity. Biological specimens were analyzed for MDPV by GC/MS and LC/MS. A White man was found dead with signs of nausea and vomiting after repeatedly abusing bath salts during a weekend binge. Femoral venous blood and urine had MDPV concentrations of 39 ng/mL and 760 ng/mL. The second fatality was a White man with a history of drug and bath salt abuse found dead at a scene in total disarray after exhibiting fits of anger and psychotic behavior. Femoral venous blood and urine had MDPV concentrations of 130 ng/mL and 3800 ng/mL. The blood and urine MDPV concentrations are within the reported recreational concentration ranges (blood 24-241 ng/mL and urine 34-3900 ng/mL). Both decedents' deaths were attributed to relevant natural causes in a setting of MDPV abuse.

At the Third Turner Resource Network Symposium, a working group presented the results of collaborative discussions about the importance of autopsy in Turner syndrome (TS). Considerable gaps in understanding the causes of death in TS can only be closed by more frequent death investigations and autopsies. The presentation included an overview of autopsy methods, strategies for utilizing autopsy, and biobanking to address research questions about TS, and the role of palliative care in the context of autopsy. This review highlights strategies to promote autopsy and tissue donation, culminating with an action plan to increase autopsy rates in the TS community.

Iris recognition is a validated and non-invasive human identification technology currently implemented for the purposes of surveillance and security (i.e. border control, schools, military). Similar to deoxyribonucleic acid (DNA), irises are a highly individualizing component of the human body. Based on a lack of genetic penetrance, irises are unique between an individual’s left and right iris and between identical twins, proving to be more individualizing than DNA. At this time, little to no research has been conducted on the use of postmortem iris scanning as a biometric measurement of identification. The purpose of this pilot study is to explore the use of iris recognition as a tool for postmortem identification. Objectives of the study include determining whether current iris recognition technology can locate and detect iris codes in postmortem globes, and if iris scans collected at different postmortem time intervals can be identified as the same iris initially enrolled. Data from 43 decedents involving 148 subsequent iris scans demonstrated a subsequent match rate of approximately 80%, supporting the theory that iris recognition technology is capable of detecting and identifying an individual’s iris code in a postmortem setting. A chi-square test of independence showed no significant difference between match outcomes and the globe scanned (left vs. right), and gender had no bearing on the match outcome. There was a significant relationship between iris color and match outcome, with blue/gray eyes yielding a lower match rate (59%) compared to brown (82%) or green/hazel eyes (88%), however, the sample size of blue/gray eyes in this study was not large enough to draw a meaningful conclusion. An isolated case involving an antemortem initial scan collected from an individual on life support yielded an accurate identification (match) with a subsequent scan captured at approximately 10 hours postmortem. Falsely rejected subsequent iris scans or "no match" results occurred in about 20% of scans; they were observed at each PMI range and varied from 19-30%. The false reject rate is too high to reliably establish non-identity when used alone and ideally would be significantly lower prior to implementation in a forensic setting; however, a "no match" could be confirmed using another method. Importantly, the data showed a false match rate or false accept rate (FAR) of zero, a result consistent with previous iris recognition studies in living individuals. The preliminary results of this pilot study demonstrate a plausible role for iris recognition in postmortem human identification. Implementation of a universal iris recognition database would benefit the medicolegal death investigation and forensic pathology communities, and has potential applications to other situations such as missing persons and human trafficking cases.

Forensic anthropologists rely on forensic evidence to estimate the postmortem interval of a decedent. This may include the study of the degree of deterioration of the human body, the life stage of insects, and the degradation of associated material evidence. Material evidence comes in many forms, and certain taphonomic processes will affect the material and must be considered when making inferences about a PMI. These include variables such as the characteristics of the soil, microorganisms, and the presence of a decaying organic material. Previous research has undertaken studies in how fabric degrades over time; however, there is no standard methodology in use. The purpose of this research project is to establish a comprehensive scoring system and description standard after analyzing the degradation of four different fabric types. This will be useful for future studies in need of a standard methodology. In addition, the methods used in this project can be applied to actual forensic cases. After retrieval, the fabric type with the highest degradation was the cotton with about 1/3 of all cotton fabric swatches demonstrating more than 50% total degradation. For all fabric types, swatches that were positioned flat tended to degrade more than those that were positioned crumpled. Cotton fabric swatches degraded more in Trench 1 and Trench 2 than the Ground Surface, however, all other fabric types demonstrated slightly more degradation on the Ground Surface than the other two Areas. Soil moisture fluctuated the most on the Ground Surface while Trench 1 and Trench 2 were able to retain more water in the soil. Overall, cotton was the only fabric type to degrade significantly enough to show how it degrades over time, while the other fabric types have longer degradation intervals that must be studied further.

Currently, forensic scientists are only able to determine time since death (or postmortem interval) up to the first 60 hours. This is based largely on insect activity. Herein, it is proposed to use the degradation of the intervertebral disc (IVD) after death to determine a relationship between the mechanical properties of cadaveric tissue and time since death in order to extend the 60-hour window. To that end, 1 fresh human spine and 6 pig spines were each separated into sections (6 human and 48 pig), with each section having one intact disc. The sections were buried, unearthed, and cleaned, leaving only the disc and bone. To determine the mechanical properties, each disc underwent three different tests: cyclic conditioning, compression, and stress relaxation testing. The Schapery collocation method was used to create a theoretical curve from the data for the experimental curve. Observations were made involving the corresponding k values of the curve. Although there are trends in the data for k values that approximate the experimental stress relaxation curve, a correlation could not be determined.

The present research examined remains found from the Winchester Site in Winchester, MA that have evidence for postmortem alteration. The author compared the assemblages from Point San Jose (Hart et al. 2019; Willey et al. 2018), Holden Chapel (Hodge 2013; Hodge et al. 2017), Medical College of Georgia (Blakley 1997; McFarlin and Wineski 1997; Terrell and McFarlin 1997), Milwaukee County Institutional Grounds (Dougherty and Sullivan 2017), Newcastle Infirmary (Chamberlain 2016), and Blockley Almshouse (Crist et al. 2017; Hynes 2005) regarding patterns in bone modification and their potential causes. The sawn assemblage consists of 1365 adult remains, 67 juvenile remains, and 13 nonhuman remains. The human adult sawn Winchester Site sample is composed of 19.7% cranial remains and 80.3% postcranial remains. The postmortem alterations found on the remains from the Winchester Site lack pathological changes surrounding them. Eight of the 17 (47.0%) nearly complete crania exhibit evidence for craniotomy. Postmortem trephinations are seen in three crania. Repetition of surgical procedure training is seen through the 349 transverse complete kerfs located on the postcranial remains. There are 125 sternal segments and 133 rib segments with evidence of sharp force trauma, potentially from thoracotomy. The postmortem alteration within the faunal assemblage can be attributed to butchery on the elements from cow, sheep, and unidentified mammal, and dissection on the elements from the dog and red fox. Implements utilized on the skeletal remains were a flat-bladed saw with 18 teeth per inch (TPI) and a trephine. The remains from the Winchester Site exhibit experimentation with kerf locations, most likely originating from surgical training practices.

In postmortem toxicology, certain cases require the examination of embalmed biological specimens to investigate the presence and potential role drugs may have played in a person’s death. Key factors, like postmortem distribution, which can be greatly affected by temperature, may alter drug concentrations in different areas of the body. In the United States, the involvement of cocaine in overdose deaths has significantly increased between 2012 and 2019 (1). The purpose of this project was to examine the stability of cocaine and its primary metabolite, benzoylecgonine, in perfused postmortem rat tissues stored at different temperatures over a one month. Twelve frozen cocaine positive rat specimens, intracardially perfused with a saline and formaldehyde solution, were received from a chronic cocaine rat study at Boston University Department of Psychological and Brain Sciences (Dr. Kathleen Kantak, Boston, MA, USA). The specimens were dissected, and the spleen, one kidney, and one lung were removed from each specimen. A fine-needle aspiration biopsy was performed on each organ to collect a time zero (T0) sample. One set of four rat specimens were stored at room temperature (20-22°C), another four were stored at refrigerator temperature (4°C), and another four were stored at freezer temperature (-20°C). A section of each organ was collected for analysis at two weeks (T1) and one month (T2). Samples underwent solid-phase extraction before liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis using a QSight 220 CR Laminar Flow Triple Quadrupole Mass Spectrometer with electrospray ionization, operated in positive ion mode (PerkinElmer, Shelton, CT, USA). Simplicity 3QTM software (PerkinElmer) was used for all data collection, analysis, and quantification. All calibration curves generated for each analyte had acceptable R2 values greater than 0.98 using a weighted linear regression model (1/x). Between T1 and T2, eight samples demonstrated a 15-873% increase in cocaine concentration and four samples had a 13-45% decrease in cocaine concentration. For benzoylecgonine, nine samples demonstrated an 18-289% increase in concentration between T1 and T2 and six samples had a 3-57% decrease in concentration. In samples collected at one month, concentration values for cocaine were highest in samples stored at freezer temperature (-20°C) and lowest in samples stored at refrigerator temperature (4°C). The highest benzoylecgonine values were found in samples stored at freezer temperature (-20°C) as well, and the lowest concentrations were in samples stored at room temperature (20-22°C). Due to the variability in analyte concentration in the organs of the intracardially perfused specimens, the impact storage conditions had on analyte stability could not be determined.