Comparison of different approaches to manage multi-site magnetic resonance spectroscopy clinical data analysis

IntroductionThe effects caused by differences in data acquisition can be substantial and may impact data interpretation in multi-site/scanner studies using magnetic resonance spectroscopy (MRS). Given the increasing use of multi-site studies, a better understanding of how to account for different scanners is needed. Using data from a concussion population, we compare ComBat harmonization with different statistical methods in controlling for site, vendor, and scanner as covariates to determine how to best control for multi-site data.MethodsThe data for the current study included 545 MRS datasets to measure tNAA, tCr, tCho, Glx, and mI to study the pediatric concussion acquired across five sites, six scanners, and two different MRI vendors. For each metabolite, the site and vendor were accounted for in seven different models of general linear models (GLM) or mixed-effects models while testing for group differences between the concussion and orthopedic injury. Models 1 and 2 controlled for vendor and site. Models 3 and 4 controlled for scanner. Models 5 and 6 controlled for site applied to data harmonized by vendor using ComBat. Model 7 controlled for scanner applied to data harmonized by scanner using ComBat. All the models controlled for age and sex as covariates.ResultsModels 1 and 2, controlling for site and vendor, showed no significant group effect in any metabolites, but the vendor and site were significant factors in the GLM. Model 3, which included a scanner, showed a significant group effect for tNAA and tCho, and the scanner was a significant factor. Model 4, controlling for the scanner, did not show a group effect in the mixed model. The data harmonized by the vendor using ComBat (Models 5 and 6) had no significant group effect in both the GLM and mixed models. Lastly, the data harmonized by the scanner using ComBat (Model 7) showed no significant group effect. The individual site data suggest there were no group differences.ConclusionUsing data from a large clinical concussion population, different analysis techniques to control for site, vendor, and scanner in MRS data yielded different results. The findings support the use of ComBat harmonization for clinical MRS data, as it removes the site and vendor effects

The adsorption of nitrobenzene over an alumina-supported palladium catalyst: an infrared spectroscopic study

As part of an on-going programme of development of an aniline synthesis catalyst suitable for operation at elevated temperatures, the geometry of the adsorption complex for nitrobenzene on a 5 wt% Pd/Al₂O₃ catalyst is investigated by infrared (IR) spectroscopy. Via an appreciation of the reduced site symmetry resulting from adsorption, application of the metal surface selection rule, and observation of in-plane modes only, the adsorption complex (Pd–nitrobenzene) at 28 °C is assigned as occurring vertically or tilted with respect to the metal surface, adopting Cₛσᵥ(yz) symmetry. Moreover, adsorption occurs via a single Pd–O bond. Single molecule DFT calculations and simulated IR spectra assist vibrational assignments but indicate a parallel adsorption geometry to be energetically favourable. The contradiction between calculated and observed structures is attributed to the DFT calculations corresponding to an isolated molecule adsorption complex, while IR spectra relate to multi molecule adsorption that is encountered during sustained catalytic turnover. Residual hydrogen from the catalyst reduction stage leads to aniline formation on the Pd surface at low nitrobenzene coverages but, on increasing nitrobenzene exposure, the aniline is forced on to the alumina support. A reaction scheme is proposed whereby the nitrobenzene adsorption geometry is inherently linked to the high aniline selectivity observed for Pd/Al₂O₃ catalysts

Structure and spectroscopy of CuH prepared via borohydride reduction

Copper(I) hydride (cuprous hydride, CuH) was the first binary metal hydride to be discovered (in 1844) and is singular in that it is synthesized in solution, at ambient temperature. There are several synthetic paths to CuH, one of which involves reduction of an aqueous solution of CuSO(4)·5H(2)O by borohydride ions. The product from this procedure has not been extensively characterized. Using a combination of diffraction methods (X-ray and neutron) and inelastic neutron scattering spectroscopy, we show that the CuH from the borohydride route has the same bulk structure as CuH produced by other routes. Our work shows that the product consists of a core of CuH with a shell of water and that this may be largely replaced by ethanol. This offers the possibility of modifying the properties of CuH produced by aqueous routes

A new role for lipocalin prostaglandin d synthase in the regulation of brown adipose tissue substrate utilization.

In this study, we define a new role for lipocalin prostaglandin D synthase (L-PGDS) in the control of metabolic fuel utilization by brown adipose tissue (BAT). We demonstrate that L-PGDS expression in BAT is positively correlated with BAT activity, upregulated by peroxisome proliferator-activated receptor γ coactivator 1α or 1β and repressed by receptor-interacting protein 140. Under cold-acclimated conditions, mice lacking L-PGDS had elevated reliance on carbohydrate to provide fuel for thermogenesis and had increased expression of genes regulating glycolysis and de novo lipogenesis in BAT. These transcriptional differences were associated with increased lipid content in BAT and a BAT lipid composition enriched with de novo synthesized lipids. Consistent with the concept that lack of L-PGDS increases glucose utilization, mice lacking L-PGDS had improved glucose tolerance after high-fat feeding. The improved glucose tolerance appeared to be independent of changes in insulin sensitivity, as insulin levels during the glucose tolerance test and insulin, leptin, and adiponectin levels were unchanged. Moreover, L-PGDS knockout mice exhibited increased expression of genes involved in thermogenesis and increased norepinephrine-stimulated glucose uptake to BAT, suggesting that sympathetically mediated changes in glucose uptake may have improved glucose tolerance. Taken together, these results suggest that L-PGDS plays an important role in the regulation of glucose utilization in vivo

Agricultural intensification and the evolution of host specialism in the enteric pathogen Campylobacter jejuni.

Modern agriculture has dramatically changed the distribution of animal species on Earth. Changes to host ecology have a major impact on the microbiota, potentially increasing the risk of zoonotic pathogens being transmitted to humans, but the impact of intensive livestock production on host-associated bacteria has rarely been studied. Here, we use large isolate collections and comparative genomics techniques, linked to phenotype studies, to understand the timescale and genomic adaptations associated with the proliferation of the most common food-born bacterial pathogen (Campylobacter jejuni) in the most prolific agricultural mammal (cattle). Our findings reveal the emergence of cattle specialist C. jejuni lineages from a background of host generalist strains that coincided with the dramatic rise in cattle numbers in the 20th century. Cattle adaptation was associated with horizontal gene transfer and significant gene gain and loss. This may be related to differences in host diet, anatomy, and physiology, leading to the proliferation of globally disseminated cattle specialists of major public health importance. This work highlights how genomic plasticity can allow important zoonotic pathogens to exploit altered niches in the face of anthropogenic change and provides information for mitigating some of the risks posed by modern agricultural systems