New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Improving Operator Situation Awareness by Phasor Measurement Unit (PMU) Data Visualization

The application of phasor measurement unit (PMU) data in the power industry is currently an area of intense interest. The key driver for PMU technology is to use the precise time sources provided by Global Positioning System (GPS) satellites to accurately measure the relative voltage and current phase angles at buses across an interconnect at a very high sampling rate. Presenting PMU data to power system operators in a format that is truly useful for them and that affords improved situation awareness (SA) and fast and accurate decision making is a particular challenge to display design. This report describes development of prototype displays of PMU data where the design criteria were derived from characteristics of the data as well as the situation awareness requirements of power system dispatchers. A prototype display that meets all these design criteria is described

Focal nonmotor versus motor seizures: The impact on diagnostic delay in focal epilepsy

Objective To test the hypothesis that people with focal epilepsy experience diagnostic delays that may be associated with preventable morbidity, particularly when seizures have only nonmotor symptoms, we compared time to diagnosis, injuries, and motor vehicle accidents (MVAs) in people with focal nonmotor versus focal seizures with motor involvement at epilepsy onset. Methods This retrospective study analyzed the enrollment data from the Human Epilepsy Project, which enrolled participants between 2012 and 2017 across 34 sites in the USA, Canada, Europe, and Australia, within 4 months of treatment for focal epilepsy. A total of 447 participants were grouped by initial seizure semiology (focal nonmotor or focal with motor involvement) to compare time to diagnosis and prediagnostic injuries including MVAs. Results Demographic characteristics were similar between groups. There were 246 participants (55%) with nonmotor seizures and 201 participants (45%) with motor seizures at epilepsy onset. Median time to diagnosis from first seizure was 10 times longer in patients with nonmotor seizures compared to motor seizures at onset (P < .001). The number and severity of injuries were similar between groups. However, 82.6% of MVAs occurred in patients with undiagnosed nonmotor seizures. Significance This study identifies reasons for delayed diagnosis and consequences of delay in patients with new onset focal epilepsy, highlighting a treatment gap that is particularly significant in patients who experience nonmotor seizures at epilepsy onset