246 research outputs found
The Ursinus College Investment Management Company Newsletter, Spring 2021
Inside this issue:
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Intellectual Disability in Children with Congenital Heart Defects in Western Australia
Introduction
Congenital heart defects (CHD) are diagnosed up to age 6 in 8-12/1,000 births annually in Western Australia. Recent improvements in management of infants with CHDs has significantly increased survival; approximately 85\% of infants with CHDs live beyond childhood. However, children with CHDs may have increased risk of life-long intellectual disabilities.
Objectives and Approach
We conducted a study of 20,997 children to determine risk of intellectual disability (ID). All singleton, live born infants with CHDs born 1983-2010 were identified from the Western Australian Register for Developmental Anomalies, a statewide birth defects registry (n=6,968). Infants without CHDs born 1983-2010 were randomly selected from birth records (n=14,029). All data were linked to the Western Australia Midwives Notification System to obtain maternal and infant information. Children with ID were identified by linkage to the statewide Intellectual Disability Exploring Answers database. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from multivariable logistic regression analyses.
Results
Of 20,997 children, 965 (4.6%) had an ID; 1.3% of children without CHDs and 11.2% of children with CHDs had an ID (P<0.001). 0.2% of children without CHDs and 0.4% of children with CHDs had autism. Three percent of children with CHDs had a known biomedical cause for ID (excluding trisomy 21) and 4.4% of children with CHDs had trisomy 21. Children with CHDs had 9 times the risk of ID compared to children without CHDs (RR=9.30; 95% CI: 7.91, 10.94). Children with CHDs almost had a twofold increased risk of autism compared to children without CHDs (RR=1.78; 95% CI: 1.07, 2.95). The greatest risk of ID among children with CHDs was associated with trisomy 21 (RR=166.0; 95% CI: 78.5, 350.8).
Conclusion/Implications
Children with CHDs have higher risk of ID than children without CHDs. Although the greatest risk for ID was for trisomy 21, children with CHDs still had increased risk of ID from other causes and all causes overall. Future research should elucidate the underlying etiology of ID in these children
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Impacts of urban microclimate on summertime sensible and latent energy demand for cooling in residential buildings of Hong Kong
The urban heat island (UHI) and urban moisture island (UMI) effect can be significant in Hong Kong due to its high-density land utilization, and this can strongly affect building energy performance. While the UHI’ energy impact has been rather intensively studied recently, the UMI effect on latent energy is still underexplored, especially for humid subtropical climate like Hong Kong. This study investigated the intensity of UHI and UMI in Hong Kong, and its impacts on the sensible and latent cooling demand of residential buildings in summer. Firstly, a ten-year weather dataset from 2004 to 2013 for the six stations selected based on the local climate zone (LCZ) scheme was analysed. The results show that the urban area of Hong Kong appears as both a heat and moisture island during summer nights but as cooling and dry islands during daytime, and the nocturnal UHI and UMI intensity vary significantly with different LCZs. Furthermore, the energy performance of a typical residential building in Hong Kong was simulated with measured weather data for the selected stations as an input. The urban building shows a higher sensible cooling demand, approximately twice that of the comparative rural one, and the latent cooling demand could be up to 96% higher. Both sensible and latent cooling energy demand decrease with increasing LCZ grades. Our study highlights that both UHI and UMI effect should be considered in the estimation of building energy in Hong Kong due to their significant impacts on the cooling energy demand
Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults
BACKGROUND: Plasma neurofilament light (NfL) is an indicator of neurodegeneration and/or neuroaxonal injury in persons with Alzheimer's disease (AD) and a wide range of other neurological disorders. Here, we characterized and compared plasma NfL concentrations in cognitively unimpaired (CU) late-middle-aged and older adults with two, one, or no copies of the APOE ε4 allele, the major genetic risk factor for AD. We then assessed plasma NfL associations with brain imaging measurements of AD-related neurodegeneration (hippocampal atrophy and a hypometabolic convergence index [HCI]), brain imaging measurements of amyloid-β plaque burden, tau tangle burden and white matter hyperintensity volume (WMHV), and delayed and total recall memory scores. METHODS: Plasma NfL concentrations were measured in 543 CU 69 ± 9 year-old participants in the Arizona APOE Cohort Study, including 66 APOE ε4 homozygotes (HM), 165 heterozygotes (HT), and 312 non-carriers (NC). Robust regression models were used to characterize plasma NfL associations with APOE ε4 allelic dose before and after adjustment for age, sex, and education. They were also used to characterize plasma NfL associations with MRI-based hippocampal volume and WMHV measurements, an FDG PET-based HCI, mean cortical PiB PET measurements of amyloid-β plaque burden and meta-region-of-interest (meta-ROI) flortaucipir PET measurements of tau tangle burden, and Auditory Verbal Learning Test (AVLT) Delayed and Total Recall Memory scores. RESULTS: After the adjustments noted above, plasma NfL levels were significantly greater in APOE ε4 homozygotes and heterozygotes than non-carriers and significantly associated with smaller hippocampal volumes (r =  - 0.43), greater tangle burden in the entorhinal cortex and inferior temporal lobes (r = 0.49, r = 0.52, respectively), and lower delayed (r =  - 0.27), and total (r =  - 0.27) recall memory scores (p < 0.001). NfL levels were not significantly associated with PET measurements of amyloid-β plaque or total tangle burden. CONCLUSIONS: Plasma NfL concentrations are associated with the APOE ε4 allele, brain imaging biomarkers of neurodegeneration, and less good recall memory in CU late-middle-aged and older adults, supporting its value as an indicator of neurodegeneration in the preclinical study of AD
Fine Mapping of the Bsr1 Barley Stripe Mosaic Virus Resistance Gene in the Model Grass Brachypodium distachyon
The ND18 strain of Barley stripe mosaic virus (BSMV) infects several lines of Brachypodium distachyon, a recently developed model system for genomics research in cereals. Among the inbred lines tested, Bd3-1 is highly resistant at 20 to 25°C, whereas Bd21 is susceptible and infection results in an intense mosaic phenotype accompanied by high levels of replicating virus. We generated an F6∶7 recombinant inbred line (RIL) population from a cross between Bd3-1 and Bd21 and used the RILs, and an F2 population of a second Bd21 × Bd3-1 cross to evaluate the inheritance of resistance. The results indicate that resistance segregates as expected for a single dominant gene, which we have designated Barley stripe mosaic virus resistance 1 (Bsr1). We constructed a genetic linkage map of the RIL population using SNP markers to map this gene to within 705 Kb of the distal end of the top of chromosome 3. Additional CAPS and Indel markers were used to fine map Bsr1 to a 23 Kb interval containing five putative genes. Our study demonstrates the power of using RILs to rapidly map the genetic determinants of BSMV resistance in Brachypodium. Moreover, the RILs and their associated genetic map, when combined with the complete genomic sequence of Brachypodium, provide new resources for genetic analyses of many other traits
The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis
The long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) maintains the integrity of the intestinal epithelial barrier and regulates local inflammation. However, its influences on intestinal microbial communities and tissue susceptibility to cancer development remain unexplored. Here, we report that MALAT1 regulates host anti-microbial response gene expression and the composition of mucosal-associated microbial communities in a region-specific manner. In the APC mutant mouse model of intestine tumorigenesis, knocking out MALAT1 results in higher polyp counts in the small intestine and colon. Interestingly, intestine polyps that developed in the absence of MALAT1 were smaller in size. These findings highlight the unexpected bivalent role of MALAT1 in restricting and promoting cancer progression at different disease stages. Among the 30 MALAT1-targets shared by both the small intestine and colon, ZNF638 and SENP8 levels are predictive of colon adenoma patient overall survival and disease-free survival. Genomic assays further revealed that MALAT1 modulates intestinal target expression and splicing through both direct and indirect mechanisms. This study expands the role of lncRNAs in regulating intestine homeostasis, microbial communities, and cancer pathogenesis
A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism
We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism
Maternal DNA Methylation Regulates Early Trophoblast Development
This work was funded by the BBSRC, Wellcome Trust, MRC, the EC Network of Excellence EpiGeneSys, the EC BLUEPRINT project, the Centre for Trophoblast Research, and CIHR (grant MOP-119357 to L.L.). M.R.B. is a Sir Henry Dale Fellow (101225/Z/13/Z), jointly funded by the Wellcome Trust and the Royal Society
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