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

Prototype Ultrahigh-Resolution Computed Tomography for Chest Imaging: Initial Human Experience

Item does not contain fulltextOBJECTIVE: The objective of this study was to evaluate a prototype, ultrahigh-resolution computed tomography offering higher reconstruction matrix (1024 x 1024) and spatial resolution (0.15 mm) for chest imaging. METHODS: Higher (1024) matrix reconstruction enabled by ultrahigh-resolution computed tomography scanner (128-detector rows; detector width, 0.25 mm; spatial resolution, 0.15 mm) was compared with conventional (512) reconstruction with image quality grading on a Likert scale (1, excellent; 5, nondiagnostic) for image noise, artifacts, contrast, small detail, lesion conspicuity, image sharpness, and diagnostic confidence. Image noise and signal-to-noise ratio were quantified. RESULTS: Diagnostic image quality was achieved for all scans on 101 patients. The 1024 reconstruction demonstrated increased image noise (20.2 +/- 4.0 vs 17.2 +/- 3.8, P < 0.001) and a worse noise rating (1.98 +/- 0.63 vs 1.75 +/- 0.61, P < 0.001) but performed significantly better than conventional 512 matrix with fewer artifacts (1.37 +/- 0.43 vs 1.50 +/- 0.48, P < 0.001), better contrast (1.50 +/- 0.56 vs 1.62 +/- 0.57, P < 0.001), small detail detection (1.06 +/- 0.19 vs 2.02 +/- 0.22, P < 0.001), lesion conspicuity (1.08 +/- 0.23 vs 2.02 +/- 0.24, P < 0.001), sharpness (1.09 +/- 0.24 vs 2.02 +/- 0.28, P < 0.001), and overall diagnostic confidence (1.09 +/- 0.25 vs 1.18 +/- 0.34, P < 0.001). CONCLUSIONS: Ultrahigh-resolution computed tomography enabled a higher reconstruction matrix and improved image quality compared with conventional matrix reconstruction, with a minor increase in noise

Validation of child behavior rating scale in Singapore (Part 2): convergent and discriminant validity

Background/Objective: In a previous study, the Child Behavior Rating Scales (CBRSs) were found to assess interpersonal social skills (IPS) and learning-related social skills (LRSS) in young Singaporean children. This study aimed to evaluate the convergent validity of the IPS scale within the CBRS and the discriminant validity of the LRSS scale within the CBRS with a dynamic occupational therapist assessment, the Evaluation of Social Interaction (ESI). Methods: Teachers of 117 Singaporean children completed the CBRS. An occupational therapist assessed these children using the naturalistic observational tool ESI. The Rasch-derived scores from the two CBRS scales were correlated with the ESI scores. Results: The IPS scale within the CBRS demonstrated moderate correlation with ESI, indicating convergent validity. The LRSS scale within the CBRS demonstrated low correlation with ESI, indicating discriminant validity. Conclusion: This study provides additional validity evidence for the two newly identified CBRS scales. Results of this study suggest the potential of these scales for use by occupational therapists to measure different types of young children's social skills. Copyrigh

Neuromuscular degeneration (nmd): a mutation on mouse chromosome 19 that causes motor neuron degeneration.

Neuromuscular degeneration, nmd, is a spontaneous autosomal recessive mutation in the mouse producing progressive hindlimb impairment caused by spinal muscular atrophy. We used an intersubspecific intercross between B6.BKs-nmd2J/+ and Mus musculus castaneus (CAST/Ei) to map the nmd mutation to mouse Chromosome (Chr) 19 with the most likely gene order: nmd-(D19Sel2, Pygm)-Cntf-Pomc2-D19Mit16-Cyp2c-Got1. nmd maps near muscle deficient, mdf, and has a very similar clinical phenotype, but allele tests and histological differences suggest that nmd is a distinct mutation at a different locus. Although closely linked, nmd recombined with the candidate genes muscle glycogen phosphorylase, Pygm, and ciliary neurotrophic factor, Cntf