19 results on '"Hooker, CA"'
Search Results
2. Design, Value and the Future of Engineering Education
- Author
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World Conference on Engineering Education for Advancing Technology (1989 : University of Sydney), Hooker, CA, and Robinson, RM
- Published
- 1989
3. Reading and language profiles among children with epilepsy.
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Macdonald KT, Hooker CA, Loblein HJ, Davis Gaillard W, Sepeta LN, and Berl MM
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- Humans, Child, Female, Male, Adolescent, Child, Preschool, Young Adult, Comprehension physiology, Language Disorders etiology, Language, Reading, Epilepsy psychology, Epilepsy complications, Language Tests
- Abstract
This study evaluated the profile of language and reading skills among children with epilepsy. We utilized a sample of children from an epilepsy database who were administered a measure of reading comprehension, excluding those whose intellectual skills were in the impaired range (N=147; age range 4-20 years, 52 % female). Additional measures that were considered within the sample included broad language skills, pre-reading skills (phonological processing, rapid naming, decoding), and basic reading skills (sight word reading, reading fluency). We further considered associations between these skills and seizure characteristics (age of onset, number of anti-seizure medications, seizure type, seizure frequency, and localization). We found that our sample performed significantly lower on all language and reading skills, on average, than normative expectations. Within our sample, relative strengths were noted in broad language skills, and relative weaknesses were found in phonological processing, rapid naming, reading fluency, word reading, and reading comprehension. We further identified a subgroup of our sample (31 %) who were characterized as struggling in reading comprehension (performing one standard deviation below the normative mean); these children exhibited a profile more consistent with non-epilepsy samples with reading disabilities/ dyslexia. Seizure variables that were associated with language and reading skills included age of onset, number of anti-seizure medications, seizure frequency, and having generalized (versus focal) seizures. These results have important implications for the identification and treatment of reading problems in children with epilepsy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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4. A Genetic Engineering Toolbox for the Lignocellulolytic Anaerobic Gut Fungus Neocallimastix frontalis .
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Hooker CA, Hanafy R, Hillman ET, Muñoz Briones J, and Solomon KV
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- Anaerobiosis, Promoter Regions, Genetic, Genetic Engineering, Neocallimastix genetics
- Abstract
Anaerobic fungi are powerful platforms for biotechnology that remain unexploited due to a lack of genetic tools. These gut fungi encode the largest number of lignocellulolytic carbohydrate active enzymes (CAZymes) in the fungal kingdom, making them attractive for applications in renewable energy and sustainability. However, efforts to genetically modify anaerobic fungi have remained limited due to inefficient methods for DNA uptake and a lack of characterized genetic parts. We demonstrate that anaerobic fungi are naturally competent for DNA and leverage this to develop a nascent genetic toolbox informed by recently acquired genomes for transient transformation of anaerobic fungi. We validate multiple selectable markers (HygR and Neo), an anaerobic reporter protein (iRFP702), enolase and TEF1A promoters, TEF1A terminator, and a nuclear localization tag for protein compartmentalization. This work establishes novel methods to reliably transform the anaerobic fungus Neocallimastix frontalis , thereby paving the way for strain development and various synthetic biology applications.
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- 2023
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5. Hydrolysis of lignocellulose by anaerobic fungi produces free sugars and organic acids for two-stage fine chemical production with Kluyveromyces marxianus.
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Hillman ET, Li M, Hooker CA, Englaender JA, Wheeldon I, and Solomon KV
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- Acids chemistry, Acids metabolism, Anaerobiosis physiology, Esters chemistry, Esters metabolism, Hydrolysis, Kluyveromyces metabolism, Lignin chemistry, Lignin metabolism, Metabolic Engineering methods, Piromyces metabolism, Sugars chemistry, Sugars metabolism
- Abstract
Development of the bioeconomy is driven by our ability to access the energy-rich carbon trapped in recalcitrant plant materials. Current strategies to release this carbon rely on expensive enzyme cocktails and physicochemical pretreatment, producing inhibitory compounds that hinder subsequent microbial bioproduction. Anaerobic fungi are an appealing solution as they hydrolyze crude, untreated biomass at ambient conditions into sugars that can be converted into value-added products by partner organisms. However, some carbon is lost to anaerobic fungal fermentation products. To improve efficiency and recapture this lost carbon, we built a two-stage bioprocessing system pairing the anaerobic fungus Piromyces indianae with the yeast Kluyveromyces marxianus, which grows on a wide range of sugars and fermentation products. In doing so we produce fine and commodity chemicals directly from untreated lignocellulose. P. indianae efficiently hydrolyzed substrates such as corn stover and poplar to generate sugars, fermentation acids, and ethanol, which K. marxianus consumed while producing 2.4 g/L ethyl acetate. An engineered strain of K. marxianus was also able to produce 550 mg/L 2-phenylethanol and 150 mg/L isoamyl alcohol from P. indianae hydrolyzed lignocellulosic biomass. Despite the use of crude untreated plant material, production yields were comparable to optimized rich yeast media due to the use of all available carbon including organic acids, which formed up to 97% of free carbon in the fungal hydrolysate. This work demonstrates that anaerobic fungal pretreatment of lignocellulose can sustain the production of fine chemicals at high efficiency by partnering organisms with broad substrate versatility., (© 2021 American Institute of Chemical Engineers.)
- Published
- 2021
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6. Cocultivation of Anaerobic Fungi with Rumen Bacteria Establishes an Antagonistic Relationship.
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Swift CL, Louie KB, Bowen BP, Hooker CA, Solomon KV, Singan V, Daum C, Pennacchio CP, Barry K, Shutthanandan V, Evans JE, Grigoriev IV, Northen TR, and O'Malley MA
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- Anaerobiosis, Animals, Bacteria classification, Bacteria growth & development, Bacteria metabolism, Fungi classification, Fungi growth & development, Gene Expression Profiling, Genome, Bacterial, Genome, Fungal, Microbiological Techniques, Antibiosis, Bacteria genetics, Fungi genetics, Fungi physiology, Rumen microbiology, Sheep microbiology
- Abstract
Anaerobic gut fungi (Neocallimastigomycetes) live in the digestive tract of large herbivores, where they are vastly outnumbered by bacteria. It has been suggested that anaerobic fungi challenge growth of bacteria owing to the wealth of biosynthetic genes in fungal genomes, although this relationship has not been experimentally tested. Here, we cocultivated the rumen bacteria Fibrobacter succinogenes strain UWB7 with the anaerobic gut fungi Anaeromyces robustus or Caecomyces churrovis on a range of carbon substrates and quantified the bacterial and fungal transcriptomic response. Synthetic cocultures were established for at least 24 h, as verified by active fungal and bacterial transcription. A. robustus upregulated components of its secondary metabolism in the presence of Fibrobacter succinogenes strain UWB7, including six nonribosomal peptide synthetases, one polyketide synthase-like enzyme, and five polyketide synthesis O-type methyltransferases. Both A. robustus and C. churrovis cocultures upregulated S -adenosyl-l-methionine (SAM)-dependent methyltransferases, histone methyltransferases, and an acetyltransferase. Fungal histone 3 lysine 27 trimethylation marks were more abundant in coculture, and heterochromatin protein-1 was downregulated. Together, these findings suggest that fungal chromatin remodeling occurs when bacteria are present. F. succinogenes strain UWB7 upregulated four genes in coculture encoding drug efflux pumps, which likely protect the cell against toxins. Furthermore, untargeted nonpolar metabolomics data revealed at least one novel fungal metabolite enriched in coculture, which may be a defense compound. Taken together, these data suggest that A. robustus and C. churrovis produce antimicrobials when exposed to rumen bacteria and, more broadly, that anaerobic gut fungi are a source of novel antibiotics. IMPORTANCE Anaerobic fungi are outnumbered by bacteria by 4 orders of magnitude in the herbivore rumen. Despite their numerical disadvantage, they are resilient members of the rumen microbiome. Previous studies mining the genomes of anaerobic fungi identified genes encoding enzymes to produce natural products, which are small molecules that are often antimicrobials. In this work, we cocultured the anaerobic fungus Anaeromyces robustus or Caecomyes churrovis with rumen bacteria Fibrobacter succinogenes strain UWB7 and sequenced fungal and bacterial active genes via transcriptome sequencing (RNA-seq). Consistent with production of a fungal defense compound, bacteria upregulated genes encoding drug efflux pumps, which often export toxic molecules, and fungi upregulated genes encoding biosynthetic enzymes of natural products. Furthermore, tandem mass spectrometry detected an unknown fungal metabolite enriched in the coculture. Together, these findings point to an antagonistic relationship between anaerobic fungi and rumen bacteria resulting in the production of a fungal compound with potential antimicrobial activity.
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- 2021
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7. Comparative genomics of the genus Roseburia reveals divergent biosynthetic pathways that may influence colonic competition among species.
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Hillman ET, Kozik AJ, Hooker CA, Burnett JL, Heo Y, Kiesel VA, Nevins CJ, Oshiro JMKI, Robins MM, Thakkar RD, Wu ST, and Lindemann SR
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- Amino Acids biosynthesis, Bacterial Proteins genetics, Clostridiales metabolism, Energy Metabolism, Gastrointestinal Microbiome, Genome, Bacterial, Humans, Phylogeny, Species Specificity, Vitamin B Complex biosynthesis, Biosynthetic Pathways, Clostridiales classification, Clostridiales genetics, Genomics methods
- Abstract
Roseburia species are important denizens of the human gut microbiome that ferment complex polysaccharides to butyrate as a terminal fermentation product, which influences human physiology and serves as an energy source for colonocytes. Previous comparative genomics analyses of the genus Roseburia have examined polysaccharide degradation genes. Here, we characterize the core and pangenomes of the genus Roseburia with respect to central carbon and energy metabolism, as well as biosynthesis of amino acids and B vitamins using orthology-based methods, uncovering significant differences among species in their biosynthetic capacities. Variation in gene content among Roseburia species and strains was most significant for cofactor biosynthesis. Unlike all other species of Roseburia that we analysed, Roseburia inulinivorans strains lacked biosynthetic genes for riboflavin or pantothenate but possessed folate biosynthesis genes. Differences in gene content for B vitamin synthesis were matched with differences in putative salvage and synthesis strategies among species. For example, we observed extended biotin salvage capabilities in R. intestinalis strains, which further suggest that B vitamin acquisition strategies may impact fitness in the gut ecosystem. As differences in the functional potential to synthesize components of biomass (e.g. amino acids, vitamins) can drive interspecies interactions, variation in auxotrophies of the Roseburia spp. genomes may influence in vivo gut ecology. This study serves to advance our understanding of the potential metabolic interactions that influence the ecology of Roseburia spp. and, ultimately, may provide a basis for rational strategies to manipulate the abundances of these species.
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- 2020
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8. Leveraging anaerobic fungi for biotechnology.
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Hooker CA, Lee KZ, and Solomon KV
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- Anaerobiosis, Animals, Biotechnology, Genome, Fungal, Fungi, Gastrointestinal Tract
- Abstract
Early-branching anaerobic fungi are critical for hydrolyzing untreated lignocellulose in the digestive tracts of large herbivorous animals. While these fungi were discovered more than 40 years ago, they remain understudied and underexploited. Recent advances in -omics technologies, however, have enabled studies that reveal significant biosynthetic potential within anaerobic fungal genomes for diverse biotechnological applications. Applications range from enhanced second-generation bioenergy platforms to improved animal health. However, developing gut fungi for these applications will require significant advances in genome engineering technologies for these organisms. Here, we review the biotechnological abilities of anaerobic fungi and highlight challenges that must be addressed to develop them for a range of biotechnological applications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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9. Hydrolysis of untreated lignocellulosic feedstock is independent of S-lignin composition in newly classified anaerobic fungal isolate, Piromyces sp. UH3-1.
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Hooker CA, Hillman ET, Overton JC, Ortiz-Velez A, Schacht M, Hunnicutt A, Mosier NS, and Solomon KV
- Abstract
Background: Plant biomass is an abundant but underused feedstock for bioenergy production due to its complex and variable composition, which resists breakdown into fermentable sugars. These feedstocks, however, are routinely degraded by many uncommercialized microbes such as anaerobic gut fungi. These gut fungi express a broad range of carbohydrate active enzymes and are native to the digestive tracts of ruminants and hindgut fermenters. In this study, we examine gut fungal performance on these substrates as a function of composition, and the ability of this isolate to degrade inhibitory high syringyl lignin-containing forestry residues., Results: We isolated a novel fungal specimen from a donkey in Independence, Indiana, United States. Phylogenetic analysis of the Internal Transcribed Spacer 1 sequence classified the isolate as a member of the genus Piromyces within the phylum Neocallimastigomycota ( Piromyces sp. UH3-1, strain UH3-1). The isolate penetrates the substrate with an extensive rhizomycelial network and secretes many cellulose-binding enzymes, which are active on various components of lignocellulose. These activities enable the fungus to hydrolyze at least 58% of the glucan and 28% of the available xylan in untreated corn stover within 168 h and support growth on crude agricultural residues, food waste, and energy crops. Importantly, UH3-1 hydrolyzes high syringyl lignin-containing poplar that is inhibitory to many fungi with efficiencies equal to that of low syringyl lignin-containing poplar with no reduction in fungal growth. This behavior is correlated with slight remodeling of the fungal secretome whose composition adapts with substrate to express an enzyme cocktail optimized to degrade the available biomass., Conclusions: Piromyces sp. UH3-1, a newly isolated anaerobic gut fungus, grows on diverse untreated substrates through production of a broad range of carbohydrate active enzymes that are robust to variations in substrate composition. Additionally, UH3-1 and potentially other anaerobic fungi are resistant to inhibitory lignin composition possibly due to changes in enzyme secretion with substrate. Thus, anaerobic fungi are an attractive platform for the production of enzymes that efficiently use mixed feedstocks of variable composition for second generation biofuels. More importantly, our work suggests that the study of anaerobic fungi may reveal naturally evolved strategies to circumvent common hydrolytic inhibitors that hinder biomass usage.
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- 2018
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10. Accuracy of PDFF estimation by magnitude-based and complex-based MRI in children with MR spectroscopy as a reference.
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Haufe WM, Wolfson T, Hooker CA, Hooker JC, Covarrubias Y, Schlein AN, Hamilton G, Middleton MS, Angeles JE, Hernando D, Reeder SB, Schwimmer JB, and Sirlin CB
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- Adolescent, Child, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Spectroscopy, Male, Prospective Studies, Reproducibility of Results, Retrospective Studies, Young Adult, Liver diagnostic imaging, Liver pathology, Magnetic Resonance Imaging methods, Non-alcoholic Fatty Liver Disease diagnostic imaging, Non-alcoholic Fatty Liver Disease pathology
- Abstract
Purpose: To assess and compare the accuracy of magnitude-based magnetic resonance imaging (MRI-M) and complex-based MRI (MRI-C) for estimating hepatic proton density fat fraction (PDFF) in children, using MR spectroscopy (MRS) as the reference standard. A secondary aim was to assess the agreement between MRI-M and MRI-C., Materials and Methods: This was a HIPAA-compliant, retrospective analysis of data collected in children enrolled in prospective, Institutional Review Board (IRB)-approved studies between 2012 and 2014. Informed consent was obtained from 200 children (ages 8-19 years) who subsequently underwent 3T MR exams that included MRI-M, MRI-C, and T
1 -independent, T2 -corrected, single-voxel stimulated echo acquisition mode (STEAM) MRS. Both MRI methods acquired six echoes at low flip angles. T2*-corrected PDFF parametric maps were generated. PDFF values were recorded from regions of interest (ROIs) drawn on the maps in each of the nine Couinaud segments and three ROIs colocalized to the MRS voxel location. Regression analyses assessing agreement with MRS were performed to evaluate the accuracy of each MRI method, and Bland-Altman and intraclass correlation coefficient (ICC) analyses were performed to assess agreement between the MRI methods., Results: MRI-M and MRI-C PDFF were accurate relative to the colocalized MRS reference standard, with regression intercepts of 0.63% and -0.07%, slopes of 0.998 and 0.975, and proportion-of-explained-variance values (R2 ) of 0.982 and 0.979, respectively. For individual Couinaud segments and for the whole liver averages, Bland-Altman biases between MRI-M and MRI-C were small (ranging from 0.04 to 1.11%) and ICCs were high (≥0.978)., Conclusion: Both MRI-M and MRI-C accurately estimated hepatic PDFF in children, and high intermethod agreement was observed., Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1641-1647., (© 2017 International Society for Magnetic Resonance in Medicine.)- Published
- 2017
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11. Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis.
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Middleton MS, Heba ER, Hooker CA, Bashir MR, Fowler KJ, Sandrasegaran K, Brunt EM, Kleiner DE, Doo E, Van Natta ML, Lavine JE, Neuschwander-Tetri BA, Sanyal A, Loomba R, and Sirlin CB
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- Adult, Area Under Curve, Biopsy, Chenodeoxycholic Acid therapeutic use, Female, Humans, Male, Middle Aged, ROC Curve, Single-Blind Method, Adiposity, Chenodeoxycholic Acid analogs & derivatives, Liver pathology, Magnetic Resonance Imaging methods, Non-alcoholic Fatty Liver Disease diagnostic imaging, Non-alcoholic Fatty Liver Disease pathology
- Abstract
Background & Aims: We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference., Methods: We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed., Results: At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0-1 vs 2-3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91-0.98), and grade 0-2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93-0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2-3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71-0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63-0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity., Conclusions: Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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12. In vivo triglyceride composition of abdominal adipose tissue measured by 1 H MRS at 3T.
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Hamilton G, Schlein AN, Middleton MS, Hooker CA, Wolfson T, Gamst AC, Loomba R, and Sirlin CB
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- Adult, Aged, Aged, 80 and over, Artifacts, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Phantoms, Imaging, Prospective Studies, Proton Magnetic Resonance Spectroscopy, Young Adult, Abdominal Fat diagnostic imaging, Intra-Abdominal Fat diagnostic imaging, Magnetic Resonance Spectroscopy, Subcutaneous Fat diagnostic imaging, Triglycerides chemistry
- Abstract
Purpose: To investigate the regional variability of adipose tissue triglyceride composition in vivo using
1 H MRS, examining potential confounders and corrections for artifacts, to allow for adipose tissue spectrum estimation., Materials and Methods:1 H magnetic resonance (MR) stimulated echo acquisition mode (STEAM) spectra were acquired in vivo at 3T from 340 adult patients (mean age 48.9 years, range 21-79 years; 172 males, 168 females; mean body mass index [BMI] 34.0, range 22-49 kg/m2 ) with known or suspected nonalcoholic fatty liver disease (NAFLD) in deep (dSCAT), surface (sSCAT) subcutaneous adipose tissue, and visceral adipose tissue (VAT). Triglyceride composition was characterized by the number of double bonds (ndb) and number of methylene-interrupted double bonds (nmidb). A subset of patients (dSCAT n = 80, sSCAT n = 55, VAT n = 194) had the acquisition repeated three times to examine the repeatability of ndb and nmidb estimation., Results: Mean ndb and nmidb showed significant (P < 0.0001) differences between depots except for dSCAT and sSCAT nmidb (dSCAT ndb 2.797, nmidb 0.745; sSCAT ndb 2.826, nmidb 0.737; VAT ndb 2.723, nmidb 0.687). All ndb and nmidb estimates were highly repeatable (VAT ndb ICC = 0.888, nmidb ICC = 0.853; sSCAT: ndb ICC = 0.974, nmidb ICC = 0.964; dSCAT: ndb ICC = 0.959, nmidb ICC = 0.948)., Conclusion: Adipose tissue composition can be estimated repeatably using1 H MRS and different fat depots have different triglyceride compositions., Level of Evidence: 2 J. MAGN. RESON. IMAGING 2017;45:1455-1463., (© 2016 International Society for Magnetic Resonance in Medicine.)- Published
- 2017
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13. Reproducibility of MR-based liver fat quantification across field strength: Same-day comparison between 1.5T and 3T in obese subjects.
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Artz NS, Haufe WM, Hooker CA, Hamilton G, Wolfson T, Campos GM, Gamst AC, Schwimmer JB, Sirlin CB, and Reeder SB
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- Adult, Body Mass Index, Echo-Planar Imaging, Female, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Liver pathology, Magnetic Resonance Spectroscopy, Male, Middle Aged, Non-alcoholic Fatty Liver Disease pathology, Protons, Regression Analysis, Reproducibility of Results, Adipose Tissue pathology, Magnetic Resonance Imaging, Obesity physiopathology
- Abstract
Purpose: To examine the reproducibility of quantitative magnetic resonance (MR) methods to estimate hepatic proton density fat-fraction (PDFF) at different magnetic field strengths., Materials and Methods: This Health Insurance Portability and Accountability Act (HIPAA)-compliant study was approved by the Institutional Review Board. Following informed consent, 25 severely obese subjects (mean body mass index [BMI]: 45 ± 4, range: 38-53 kg/m(2) ) were scanned at 1.5T and 3T on the same day. Two confounder-corrected multiecho chemical shift-encoded gradient-echo-based imaging methods were acquired to estimate PDFF over the entire liver: 3D complex-based (MRI-C) and 2D magnitude-based (MRI-M) MRI. Single-voxel MR spectroscopy (MRS) was performed in the right liver lobe. Using linear regression, pairwise comparisons of estimated PDFF were made between methods (MRI-C, MRI-M, MRS) at each field strength and for each method across field strengths., Results: 1.5T vs. 3T regression analyses for MRI-C, MRI-M, and MRS PDFF measurements yielded R(2) values of 0.99, 0.97, and 0.90, respectively. The best-fit line was near unity (slope(m) = 1, intercept(b) = 0), indicating excellent agreement for each case: MRI-C (m = 0.92 [0.87, 0.99], b = 1.4 [0.7, 1.8]); MRI-M (m = 1.0 [0.90, 1.08], b = -1.4 [-2.4, -0.5]); MRS (m = 0.98 [0.82, 1.15], b = 1.2 [-0.2, 3.0]). Comparing MRI-C and MRI-M yielded an R(2) = 0.98 (m = 1.1 [1.02, 1.16], b = -1.8 [-2.8, -1.1]) at 1.5T, and R(2) = 0.99 (m = 0.98 [0.93, 1.03], b = 1.2 [0.7, 1.7]) at 3T., Conclusion: This study demonstrates that PDFF estimation is reproducible across field strengths and across two confounder-corrected MR-based methods., (© 2015 Wiley Periodicals, Inc.)
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- 2015
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14. Higher extracellular fluid volume in women is concealed by scaling to body surface area.
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Peters AM, Seshadri N, Neilly MD, Perry L, Hooker CA, Howard B, Sobnack R, Irwin A, Dave S, Snelling H, Gruning T, Patel NH, Shabo G, Williams N, Barnfield MC, and Lawson RS
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- Adult, Algorithms, Body Composition, Body Mass Index, Body Weight, Female, Glomerular Filtration Rate, Humans, Kidney Transplantation, Living Donors, Male, Middle Aged, Reference Values, Sex Characteristics, Body Surface Area, Extracellular Fluid metabolism
- Abstract
Objective: The objective was to assess body surface area (BSA) for scaling extracellular fluid volume (ECV) in comparison with estimated lean body mass (LBM) and total body water (TBW) across a range of body mass indices (BMI)., Methods: This was a multi-centre study from 15 centres that submitted raw data from routine measurement of GFR in potential kidney transplant donors. There were 819 men and 1059 women in total. ECV was calculated from slope-intercept and slope-only measurements of GFR. ECV was scaled using two methods: Firstly, division of ECV by the scaling variable (ratio method), and secondly the regression method of Turner and Reilly. Subjects were placed into five BMI groups: < 20, 20-24.9, 25-29.9, 30-34.9, and 35 + kg/m(2). LBM and TBW were estimated from previously published, gender-specific prediction equations., Results: Ratio and regression scaling gave almost identical results. ECV scaled to BSA by either method was higher in men in all BMI groups but ECV scaled to LBM and TBW was higher in women. There was, however, little difference between men and women in respect to ECV per unit weight in any BMI group, even though women have 10% more adipose tissue. The relations between TBW and BSA and between LBM and BSA, but not between LBM and TBW, were different between men and women., Conclusion: Lean tissue in women contains more extracellular water than in men, a difference that is obscured by scaling to BSA. The likely problem with BSA is its insensitivity to body composition.
- Published
- 2013
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15. Gene therapy researchers' assessments of risks and perceptions of risk acceptability in clinical trials.
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Deakin CT, Alexander IE, Hooker CA, and Kerridge IH
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- Clinical Trials as Topic, Decision Making, Humans, Research Personnel, Genetic Therapy adverse effects, Risk Assessment methods
- Abstract
Although recent clinical trials have demonstrated the increasing promise of gene therapy, they have also illustrated the difficulties of assessing risks, given the inherent uncertainty of trial outcomes. An international survey was conducted to investigate gene therapy researchers' perceptions and assessments of risks in clinical trials. Data from respondents (n = 156) demonstrated researchers' perceptions of clinical context and the strength of preclinical evidence strongly influenced risk assessments and judgments of acceptable risk levels. Professional experience in clinical care, and particularly care of children, predicted favorable attitudes toward nonanimal preclinical models and trial initiation when sub-optimal treatments were available. The potential for adverse events to impact negatively on the gene therapy field and on public trust were relevant considerations when planning a trial. Decisions about clinical trials appear to be influenced not only by the clinical context and preclinical evidence, but also subjective factors reflecting the experience of researchers, value-judgments about risk and benefit, and attitudes toward preclinical models, uncertainty, adverse events, and the perceived needs of patients. It is clear that risk assessment in clinical research involves moral and scientific judgment. Identifying moral assumptions and qualitative assessments underpinning the design and conduct of research may facilitate future decision-making in clinical trials.
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- 2013
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16. Extracellular fluid volume and glomerular filtration rate in 1878 healthy potential renal transplant donors: effects of age, gender, obesity and scaling.
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Peters AM, Perry L, Hooker CA, Howard B, Neilly MD, Seshadri N, Sobnack R, Irwin A, Snelling H, Gruning T, Patel NH, Lawson RS, Shabo G, Williams N, Dave S, and Barnfield MC
- Subjects
- Adult, Age Factors, Aged, Body Mass Index, Extracellular Fluid diagnostic imaging, Female, Follow-Up Studies, Humans, Kidney Function Tests, Male, Middle Aged, Prognosis, Prospective Studies, Radionuclide Imaging, Retrospective Studies, Sex Factors, Chromium Radioisotopes, Extracellular Fluid physiology, Glomerular Filtration Rate, Kidney Transplantation, Obesity complications, Tissue Donors
- Abstract
Unlabelled: Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects., Methods: This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV., Results: ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (<30 years) had higher GFR than young men but the reverse was recorded in the elderly (>65 years). There was no difference in GFR between obese (BMI>30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable., Conclusion: There are several significant differences in GFR and ECV between healthy men and women.
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- 2012
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17. The reliability of glomerular filtration rate measured from plasma clearance: a multi-centre study of 1,878 healthy potential renal transplant donors.
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Peters AM, Howard B, Neilly MD, Seshadri N, Sobnack R, Hooker CA, Irwin A, Snelling H, Gruning T, Perry L, Patel NH, Lawson RS, Shabo G, Williams N, Dave S, and Barnfield MC
- Subjects
- Adult, Aged, Benchmarking, Body Mass Index, Body Weight, Extracellular Fluid metabolism, Female, Humans, Male, Metabolic Clearance Rate, Middle Aged, Reproducibility of Results, Retrospective Studies, Sex Factors, Young Adult, Glomerular Filtration Rate, Health, Kidney Transplantation, Living Donors
- Abstract
Purpose: The objective of the study was to undertake a clinical audit of departmental performance in the measurement of glomerular filtration rate (GFR) using the coefficient of variation (CV) of extracellular fluid volume (ECFV) as the benchmark. ECFV is held within narrow limits in healthy subjects, narrower than GFR, and should therefore have a low CV., Methods: Fifteen departments participated in this retrospective study of healthy renal transplant donors. Data were analysed separately for men (n ranged from 28 to 115 per centre; total = 819) and women (n = 28-146; 1,059). All centres used the slope-intercept method with blood sample numbers ranging from two to five. Subjects did not fast prior to GFR measurement. GFR was scaled to body surface area (BSA) and corrected for the single compartment assumption. GFR scaled to ECFV was calculated as the terminal slope rate constant and corrected for the single compartment assumption. ECFV/BSA was calculated as the ratio of GFR/BSA to GFR/ECFV., Results: The departmental CVs of ECFV/BSA and GFR/BSA ranged from 8.3 to 25.8% and 12.8 to 21.9%, respectively, in men, and from 9.6 to 21.1% and 14.8 to 23.7%, respectively, in women. Both CVs correlated strongly between men and women from the same centre, suggesting department-specific systematic errors. GFR/BSA was higher in men in 14 of 15 centres, whereas GFR/ECFV was higher in women in 14 of 15 centres. Both correlated strongly between men and women, suggesting regional variation in GFR., Conclusion: The CV of ECFV/BSA in normal subjects is a useful indicator of the technical robustness with which GFR is measured and, in this study, indicated a wide variation in departmental performance.
- Published
- 2012
- Full Text
- View/download PDF
18. Optimization and assessment of quantitative 124I imaging on a Philips Gemini dual GS PET/CT system.
- Author
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Gregory RA, Hooker CA, Partridge M, and Flux GD
- Subjects
- Calibration, Iodine Radioisotopes, Photons, Positron-Emission Tomography instrumentation, Reproducibility of Results, Scattering, Radiation, Sensitivity and Specificity, Time Factors, Tomography, X-Ray Computed instrumentation, Positron-Emission Tomography methods, Tomography, X-Ray Computed methods
- Abstract
Purpose: Quantitative (124)I PET imaging is challenging as (124)I has a complex decay scheme. In this study the performance of a Philips Gemini dual GS PET/CT system was optimized and assessed for (124)I., Methods: The energy window giving the maximum noise equivalent count rate (NECR) and NEMA 2001-NU2 image quality were measured. The activity concentration (AC) accuracy of images calibrated using factors from (18)F and (124)I decaying source measurements were investigated., Results: The energy window 455-588 keV gave the maximum NECR of 9.67 kcps for 233 MBq. (124)I and (18)F image quality was comparable, although (124)I background variability was increased. The average underestimation in AC in (124)I images was 17.9 +/- 2.9% for nonuniform background and 14.7 +/- 2.9% for single scatter simulation (SSS) subtraction scatter correction. At 224 MBq the underestimation was 10.8 +/- 11.3%, which is comparable to 7.7 +/- 5.3% for (18)F, but increased with decreasing activity., Conclusions: The best (124)I PET quantitative accuracy was achieved for the optimized energy window, using SSS scatter correction and calibration factors from decaying (124)I source measurements. The quantitative accuracy for (124)I was comparable to that for (18)F at high activities of 224 MBq but diminishing with decreasing activity. Specific corrections for prompt gamma-photons may further improve the quantitative accuracy.
- Published
- 2009
- Full Text
- View/download PDF
19. Environmental quality and environmental policy: a challenge to the future of occupational therapy.
- Author
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Hooker CA
- Subjects
- Environment, Occupational Therapy
- Published
- 1972
- Full Text
- View/download PDF
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