A Swiss collaborative exercise for Disaster Victim Identification (DVI): Covering situations with different levels of complexity.

The identification of victims of a disaster (DVI) requires the collaboration of different specialists. Within a DVI context, DNA analyses often play an important role. Consequently, forensic genetic laboratories should be prepared to cope with DVI situations, as this can involve large-scale DNA profile comparisons. Six forensic genetic laboratories from Switzerland participated in an exercise where supposedly a plane had crashed. The goal of the exercise was to monitor participants use of dedicated software with ground truth cases and to make them aware of the existence of particular situations that may occur in real cases. For assigning the value of the comparison of the DNA profiles, all participating laboratories used the DVI module of Familias v3.2.1 In addition, one of the 6 laboratories used the Pedigree Searcher from CODIS v7.0. The data (AmpFlSTR® NGM SElect™ profiles) were generated to challenge the participating laboratories: cases with first, second degree biological parents, mutation events, as well as non-paternity cases were included. This study shows that the majority of the participants used the software in an appropriate way. However, a few misleading conclusions were detected for the most challenging situations. These errors belonged to one of the following categories: false pedigree, false association using the higher LR, misleading contextual information (false paternity) and not clustering family members. Specific recommendations are provided in order to reduce misuse of the software and the risk of misinterpretations by using all the relevant information.

Sampling touch DNA from human skin following skin-to-skin contact in mock assault scenarios-A comparison of nine collection methods.

Collection of touch DNA from an offender on the victim's skin can provide relevant evidence for investigations of criminal cases. Therefore, the choice of the optimal sample collection method is crucial. In this study, we investigated the recovery of STR profiles from touch DNA on human skin by comparing nine different collection methods: the dry and wet cotton swabs in three different movements, the double-swab (wet-dry) method, the wet and dry Copan FLOQSwabs™, and the Scene Safe FAST™ minitapes. Mock assault scenarios were conducted with a male offender grasping the forearms of a female victim. Samples were collected from the assaulted area of the victim's skin, and the recovery of the offender's STR profile was evaluated. Our results indicate that the different swabs and swabbing techniques did not have a distinct impact on the STR recovery; however, the lowest STR recovery was achieved with Scene Safe FAST™ minitapes. In addition, we compared the double-swab method to the single-swab method by analyzing the DNA quantity of the wet and dry swabs separately. We found on average 13.7% more offender DNA using the double-swab method, but this did not translate into higher STR recovery. Our findings indicate that several methods perform equally well when collecting touch DNA from human skin, although SceneSafe FAST™ minitapes seem to be the least adequate for this purpose.

Persistence and detection of touch DNA and blood stain DNA on pig skin exposed to water.

As it is unclear if and how long DNA evidence can persist on submerged skin, we examined the potential for recovery of touch DNA and blood stain DNA from skin samples immersed in different aquatic environments and temperatures for forensic purposes in this proof-of-concept study. We used pig skin, either smeared with human blood or held firmly for 30 s by two test-persons, before immersing it in either cold, room-temperature or warm water as well as in a stream and a pond for up to seven days prior to DNA testing. The samples were then typed at 16 STR loci. Cold water samples yielded the most promising results, as shown by the recovery of the full set of 16 reproducible STR loci from the touch DNA sample of one test-person after 7 days. For blood stains, we were able to recover all 16 reproducible STRs after 2 days. Room-temperature water and warm water yielded varying results for both blood stain DNA and touch DNA. For pond and stream samples, DNA recovery was possible only within two days. While the pond and stream samples were at relatively cold temperatures, DNA recovery may have been affected by the presence of water insects and snails in the pond and mud in the stream. Our findings show the potential of using immersed samples, particularly those immersed in cold water, as we could detect a complete DNA profile from blood stains and from touch DNA after several days. Our study opens the way for future in-depth studies, examining larger datasets and a wider range of conditions.

Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia.

Drug sensitivity and resistance testing on diagnostic leukemia samples should provide important functional information to guide actionable target and biomarker discovery. We provide proof of concept data by profiling 60 drugs on 68 acute lymphoblastic leukemia (ALL) samples mostly from resistant disease in cocultures of bone marrow stromal cells. Patient-derived xenografts retained the original pattern of mutations found in the matched patient material. Stromal coculture did not prevent leukemia cell cycle activity, but a specific sensitivity profile to cell cycle-related drugs identified samples with higher cell proliferation both in vitro and in vivo as leukemia xenografts. In patients with refractory relapses, individual patterns of marked drug resistance and exceptional responses to new agents of immediate clinical relevance were detected. The BCL2-inhibitor venetoclax was highly active below 10 nM in B-cell precursor ALL (BCP-ALL) subsets, including MLL-AF4 and TCF3-HLF ALL, and in some T-cell ALLs (T-ALLs), predicting in vivo activity as a single agent and in combination with dexamethasone and vincristine. Unexpected sensitivity to dasatinib with half maximal inhibitory concentration values below 20 nM was detected in 2 independent T-ALL cohorts, which correlated with similar cytotoxic activity of the SRC inhibitor KX2-391 and inhibition of SRC phosphorylation. A patient with refractory T-ALL was treated with dasatinib on the basis of drug profiling information and achieved a 5-month remission. Thus, drug profiling captures disease-relevant features and unexpected sensitivity to relevant drugs, which warrants further exploration of this functional assay in the context of clinical trials to develop drug repurposing strategies for patients with urgent medical needs.