German Air Force Centre of Aerospace Medicine Molecular pathology in aircraft accident investigations In co-operation with: Dr. Michael J. Schwerer, Lt. Col. Anatomic Pathologist, Forensic Pathologist, Institute of Forensic Medicine Aeromedical Examiner (class 1, military), Ludwig-Maximilians-University, Branch I 4 – Aircraft Accident Investigation, Munich, Germany Fuerstenfeldbruck, Germany Head: Prof. Dr. M. Graw 1 2 4 . 0 1 . 2 0 1 9
NATO Restricted Disclosure statement • I have no financial relationships to disclose. • I will not discuss any off-label use and/or investigational use in my presentation. 2 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Background Otto Lilienthal † 1896 Actual Airliner Crash - No fatalities 3 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Background International Civil Aviation Organization ICAO Annex 13: Aircraft Accident and Incident Investigation Founded on 7 th December 1944 4 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Background The ICAO Annex 13 „Aircraft accident and incident investigation“ requires the assessment of aircraft mishaps to increase flight safety and to prevent future accidents. • • Included in European law: Included in German national law: VOEU996/2010. Flugunfalluntersuchungsgesetz; FlUUG 1998. Medical investigation carried out in institutes for forensic pathology Technical investigation carried out by the by order of public „Bundesstelle für Flugunfalluntersuchung“ prosecutors. as an independent federal agency. 5 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Background German Air Force F104G „Starfighter“ • 900 aircraft ordered • 292 aircraft accidents • 116 pilots killed 6 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Aircraft accident investigation Forensic medical The basic questions in examination includes: the reconstruction of the mishap are: • Crash site • investigation Was the pilot alive at the moment of • External loss of control? inspection and • Occured a sudden forensic autopsy incapacitation of • Identification the pilot? using DNA-analysis • Did any kind of pre-existing • Toxicology to disease cause the confirm or exclude loss of control? illicit substances 7 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted (Forensic) Pathology in mishap investigation The basic questions in These questions the reconstruction of remain unanswered the mishap are: in autopsy alone in • Was the pilot alive the majority of cases. at the moment of loss of control? • Occured a sudden incapacitation of the pilot? • Did any kind of pre-existing disease cause the loss of control? 8 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted (Forensic) Pathology in mishap investigation Additional techniques usually involve microscopy/histology. However, these methods require sufficient qualitiy of available tissues. 9 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted (Molecular) Pathology in mishap investigation 1 0 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted (Molecular) Pathology in mishap investigation 1 1 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Aims and methods A literature review was carried out to look for new techniques in clinical pathology, which can also be used in the investigation of aircraft accidents. Own results from the implementation of these new techniques in forensic pathology practice are demonstrated. 1 2 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of pathogens Demonstration of the presence of Aeromonas species in skin wounds in clinical pathology and in veterinary medicine. Identification of the same bacteria in the peripheral blood/ deep muscles of the lower limbs is diagnostic for drowning. 1 3 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of pathogens „Cold case“ – Aircraft accident in the Lake Constance with 7 persons killed in 1994. Identification of the same bacteria in the peripheral blood/ deep muscles of the lower limbs is diagnostic for drowning. No macroscopic or histologic signs of drowning. 1 4 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of manifest heart disease Hypertrophic heart with penetrating injury from rib fracture. Hematoxylin-eosin - staining CD 56 - IHC White scar Fibronectin - IHC tissue from infarction (formalin- fixed organ). C 5b-9 - IHC 1 5 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of latent heart disease DNA degrades into short fragments. When the fragments are too short, primer annealing to the target sequence and strand elongation is impossible. 1 6 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of latent heart disease One solution investigating material with degraded DNA: Detection of the epigenetic regulation of gene expression investigating CpG-methylation in short sequences in the promotor region of genes as well as short Methylation analysis using pyrosequencing. microRNAs. MicroRNA analysis employing SybrGreen-based real-time PCR. 1 7 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of latent Heart Disease 1 8 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of latent heart disease 1 9 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of latent heart disease Hypertrophic heart with penetrating injury from rib racture. White scar tissue from infarction (formalin- fixed organ). 2 0 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Diagnosis of latent heart disease Applicable in living patients to detect e.g. tumor markers or other disease-related spill of DNA or microRNA in the bloodstream. „Liquid biopsy technique“ Applicable also in blood samples from deceased persons. Informative e.g. of disease related markers present prior to an accident event. 2 1 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Further applications Markers for other aeromedical flieds of interest including Markers for lung damage, • Circadian rhythm and e.g. in fighter pilots using performance positive pressure breathing. • Fatigue • Mood disorders • White matter lesions Markers for vascular damage, e.g. in flyers wearing anti-G-suits. 2 2 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted CpG-methylation in SFTP-promotor Methylation in muscle tissue: • 93% • 70% • 85% • 67% Methylation in lung tissue: • 71% • 46% • 54% • 53% 2 3 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted CpG-methylation in SFTP-promotor Methylation in liquid biopsy: • 79% • 59% • 69% • 66% 2 4 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Summary With these recently developed techniques molecular pathology made ist way into (scientific) aerospace medicine. ? 2 5 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
NATO Restricted Thank you very much for your attention. 2 6 2 4 . 0 1 . 2 0 1 9 A i r F o r c e C e n t r e o f A e r o s p a c e M e d i c i n e VOLANTI SUBVENIMUS
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