The 2018 California Wildfires: Integration of Rapid DNA to Dramatically Accelerate Victim Identification.

In November 2018, Butte County, California, was decimated by the Camp Fire, the deadliest wildfire in state history. Over 150,000 acres were destroyed, and at its peak, the fire consumed eighty acres per minute. The speed and intensity of the oncoming flames killed scores of people, and weeks before the fire was contained, first responders began searching through the rubble of 18,804 residences and commercial buildings. As with most mass disasters, conventional identification modalities (e.g., fingerprints, odontology, hardware) were utilized to identify victims. The intensity and duration of the fire severely degraded most of the remains, and these approaches were useful in only 22 of 84 cases. In the past, the remaining cases would have been subjected to conventional DNA analysis, which may have required months to years. Instead, Rapid DNA technology was utilized (in a rented recreational vehicle outside the Sacramento morgue) in the victim identification effort. Sixty-nine sets of remains were subjected to Rapid DNA Identification and, of these, 62 (89.9%) generated short tandem repeat profiles that were subjected to familial searching; essentially all these profiles were produced within hours of sample receipt. Samples successfully utilized for DNA identification included blood, bone, liver, muscle, soft tissue of unknown origin, and brain. In tandem with processing of 255 family reference samples, 58 victims were identified. This work represents the first use of Rapid DNA Identification in a mass casualty event, and the results support the use of Rapid DNA as an integrated tool with conventional disaster victim identification modalities.

A Case of Contested Cremains Analyzed Through Metric and Chemical Comparison.

Since the 1980s, cremation has become the fastest growing area of the U.S. funeral industry. At the same time, the number of litigations against funeral homes and cremation facilities has increased. Forensic anthropologists are often asked to determine whether the contents of an urn are actually cremated bone, and to address questions regarding the identity of the remains. This study uses both metric and chemical analyses for resolving a case of contested cremains. A cremains weight of 2021.8 g was predicted based on the decedent's reported stature and weight. However, the urn contents weighed 4173.5 g. The urn contents also contained material inconsistent with cremains (e.g., moist sediment, stones, ferrous metal). Analysis using XRD and SEM demonstrated that the urn contained thermally altered bone as well as inorganic material consistent with glass fiber cement. Although forensically challenging, cremains cases such as this one can be resolved using a multidisciplinary approach.

Osteogenic effects of a potent Src-over-Abl-selective kinase inhibitor in the mouse.

Src-null mice have higher bone mass because of decreased bone resorption and increased bone formation, whereas Abl-null mice are osteopenic, because of decreased bone formation. Compound I, a potent inhibitor of Src in an isolated enzyme assay (IC(50) 0.55 nM) and a Src-dependent cell growth assay, with lower activity on equivalent Abl-based assays, potently, but biphasically, accelerated differentiation of human mesenchymal stem cells to an osteoblast phenotype (1-10 nM). Compound I (≥0.1 nM) also activated osteoblasts and induced bone formation in isolated neonatal mouse calvariae. Compound I required higher concentrations (100 nM) to inhibit differentiation and activity of osteoclasts. Transcriptional profiling (TxP) of calvaria treated with 1 µM compound I revealed down-regulation of osteoclastic genes and up-regulation of matrix genes and genes associated with the osteoblast phenotype, confirming compound I's dual effects on bone resorption and formation. In addition, calvarial TxP implicated calcitonin-related polypeptide, ß (ß-CGRP) as a potential mediator of compound I's osteogenic effect. In vivo, compound I (1 mg/kg s.c.) increased vertebral trabecular bone volume 21% (microcomputed tomography) in intact female mice. Increased trabecular volume was also detected histologically in a separate bone, the femur, particularly in the secondary spongiosa (100% increase), which underwent a 171% increase in bone formation rate, a 73% increase in mineralizing surface, and a 59% increase in mineral apposition rate. Similar effects were observed in ovariectomized mice with established osteopenia. We conclude that the Src inhibitor compound I is osteogenic, presumably because of its potent stimulation of osteoblast differentiation and activation, possibly mediated by ß-CGRP.

(1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine: a wingless beta-catenin agonist that increases bone formation rate.

A high-throughput screening campaign to discover small molecule leads for the treatment of bone disorders concluded with the discovery of a compound with a 2-aminopyrimidine template that targeted the Wnt beta-catenin cellular messaging system. Hit-to-lead in vitro optimization for target activity and molecular properties led to the discovery of (1-(4-(naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl)methanamine (5, WAY-262611). Compound 5 has excellent pharmacokinetic properties and showed a dose dependent increase in the trabecular bone formation rate in ovariectomized rats following oral administration.