Multimodal characterization of the late effects of traumatic brain injury: a methodological overview of the Late Effects of Traumatic Brain Injury Project

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer’s and Parkinson’s disease (AD and PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional MRI, and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study

Design of experiment study on hardness variations in friction stir welding of AM60 Mg alloy

Identification of process parameters, their effects and contributions to the outcomes of the system using experimental approach could be a daunting, time consuming, and costly course. Using proper statistical methods, i.e., Taguchi method, could significantly reduce the number of required experiments and statistical significance of the parameter can be identified. Friction stir welding is one of those welding techniques with many parameters which have different effects on the quality of the welds. In friction stir welding the tool rotational speed (RPM) and transverse speed (mm/min) influence the strength (i.e., hardness distribution) of the stirred zone. In this study, these two factors are investigated to determine the effect they will have on the hardness in the stirred zone of the friction stir welds and how the two factors are related to one another for as-cast magnesium alloy AM60 with nominal chemical composition of Mg- (5.5–6.5) Al- (0.24–0.6) Mn- 0.22Zn–0.1Si. Experimental data was taken at three different tool rotational speeds and three different transverse speeds. The data obtained was then analyzed using a 32 factorial design to find the contribution of these parameters. It was determined that both tool rotational speed and transverse speed possess significant effects on the stir zone hardness. Also, the interactions between the two factors were statistically assessed. Keywords: AM60 Mg alloy, Design of experiment (DOE), Statistical method, Friction stir weldin