Cerebral Small Vessel Disease: Cognition, Mood, Daily Functioning, and Imaging Findings from a Small Pilot Sample

Cerebral small vessel disease, a leading cause of cognitive decline, is considered a relatively homogeneous disease process, and it can co-occur with Alzheimer's disease. Clinical reports of magnetic resonance imaging (MRI)/computed tomography and single photon emission computed tomography (SPECT) imaging and neuropsychology testing for a small pilot sample of 14 patients are presented to illustrate disease characteristics through findings from structural and functional imaging and cognitive assessment. Participants showed some decreases in executive functioning, attention, processing speed, and memory retrieval, consistent with previous literature. An older subgroup showed lower age-corrected scores at a single time point compared to younger participants. Performance on a computer-administered cognitive measure showed a slight overall decline over a period of 8–28 months. For a case study with mild neuropsychology findings, the MRI report was normal while the SPECT report identified perfusion abnormalities. Future research can test whether advances in imaging analysis allow for identification of cerebral small vessel disease before changes are detected in cognition

Exergetic Analysis of a Cryogenic Air Separation Unit

This case study analyzes a cryogenic air separation unit (ASU) with a production of V˙O2=58,300 [m3Nh] of gaseous oxygen with a concentration greater than 98.5%, operating in Romania on a steel plant platform. The goal of the paper is to provide an extensive model of exergetic analysis that could be used in an optimization procedure when decisional parameters are changed or structural design modifications are implemented. For each key part of the Air Separation Unit, an exergetic product and fuel were defined and, based on their definition, the coefficient of performance of each functional zone was calculated. The information about the magnitude of the exergetic losses offers solutions for their future recovery. The analysis of the exergy destructions suggests when it is worth making a larger investment. The exergetic analysis of the compression area of the ASU points out an exergy destruction and loss of 37% from the total plant’s electrical energy input. The exergy loss with the heat transferred to the cooling system of compressors can be recovered; for the exergy destruction portion, the challenge between investment and operating costs should be considered. The exergy destruction of the air separation columns found the High Pressure Column (HPC) to be more destructive than the Low Pressure Column. The share of the exergy destruction in the total plant’s electrical energy input is 8.3% for the HPC. The local COP of the HPC, calculated depending on the total exergy of the local product and fuel, is 62.66%. The calculus of the air separation column is performed with the ChemSep simulator

Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD

Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism

Summary We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD

Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neuro-developmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD