4 research outputs found
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Cerebral Microdialysate Metabolite Monitoring using Mid-infrared Spectroscopy.
Funder: Wellcome TrustThe brains of patients suffering from traumatic brain-injury (TBI) undergo dynamic chemical changes in the days following the initial trauma. Accurate and timely monitoring of these changes is of paramount importance for improved patient outcome. Conventional brain-chemistry monitoring is performed off-line by collecting and manually transferring microdialysis samples to an enzymatic colorimetric bedside analyzer every hour, which detects and quantifies the molecules of interest. However, off-line, hourly monitoring means that any subhourly neurochemical changes, which may be detrimental to patients, go unseen and thus untreated. Mid-infrared (mid-IR) spectroscopy allows rapid, reagent-free, molecular fingerprinting of liquid samples, and can be easily integrated with microfluidics. We used mid-IR transmission spectroscopy to analyze glucose, lactate, and pyruvate, three relevant brain metabolites, in the extracellular brain fluid of two TBI patients, sampled via microdialysis. Detection limits of 0.5, 0.2, and 0.1 mM were achieved for pure glucose, lactate, and pyruvate, respectively, in perfusion fluid using an external cavity-quantum cascade laser (EC-QCL) system with an integrated transmission flow-cell. Microdialysates were collected hourly, then pooled (3-4 h), and measured consecutively using the standard ISCUSflex analyzer and the EC-QCL system. There was a strong correlation between the compound concentrations obtained using the conventional bedside analyzer and the acquired mid-IR absorbance spectra, where a partial-least-squares regression model was implemented to compute concentrations. This study demonstrates the potential utility of mid-IR spectroscopy for continuous, automated, reagent-free, and online monitoring of the dynamic chemical changes in TBI patients, allowing a more timely response to adverse brain metabolism and consequently improving patient outcomes
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Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits - the Hispanic/Latino Anthropometry Consortium
Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely-imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (Stage 1, n=59,771) and generalized our findings in 9 additional studies (HISLA Stage 2, n=10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA Stage 1 and existing consortia of European and African ancestries. In our HISLA Stage 1+2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified three secondary signals for BMI, 28 for height, and two for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification
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Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium
[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.]
Recommended from our members
Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.
Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification