Editorial: Metabolic estimates during glucose challenge tests and continuous glucose monitoring-Innovative and broad approaches to assessing glucose and insulin metabolism in diverse populations.
Editorial: Metabolic estimates during glucose challenge tests and continuous glucose monitoring-Innovative and broad approaches to assessing glucose and insulin metabolism in diverse populations.
Project description:Microcrystal electron diffraction (MicroED) has emerged as a powerful technique for unraveling molecular structures from microcrystals too small for X-ray diffraction. However, a significant hurdle arises with plate-like crystals that consistently orient themselves flat on the electron microscopy grid. If the normal of the plate correlates with the axes of the crystal lattice, the crystal orientations accessible for measurement are restricted because the crystal cannot be arbitrarily rotated. This limits the information that can be acquired, resulting in a missing cone of information. We recently introduced a novel crystallization strategy called suspended drop crystallization and proposed that crystals in a suspended drop could effectively address the challenge of preferred crystal orientation. Here we demonstrate the success of the suspended drop approach in eliminating the missing cone in two samples that crystallize as thin plates: bovine liver catalase and the SARS‑CoV‑2 main protease (Mpro). This innovative solution proves indispensable for crystals exhibiting systematic preferred orientations, unlocking new possibilities for structure determination by MicroED.
Project description:Few studies have assessed the accuracy of the FreeStyle Libre Pro (FLP) continuous glucose monitor for estimating plasma glucose (PG) in non-diabetic children.ObjectiveDetermine the accuracy of FLP compared to PG during OGTT in healthy children.SubjectsChildren (7-11.99 years) with healthy weight and overweight/obesity (n = 33; 52% male).MethodsParticipants wore the FLP before and during a 2-hour OGTT; PG was measured at 30 minutes intervals. Potential systematic- and magnitude-related biases for FLP vs PG were examined.ResultsFLP 15-minute averages and PG were correlated at most timepoints during OGTT (r2 = 0.35-0.69, P's < .001 for time point 30-120 minutes) and for PG area under the curve (AUC) (r2 = 0.65, P < .0001). There were no systematic biases as assessed by Bland-Altman analyses for FLP AUC or for FLP at each OGTT timepoint. However, for fasting glucose, a significant magnitude bias was noted (r2 = 0.38, P < .001), such that lower PG was underestimated, and higher PG was overestimated by FLP readings; further, there was poor correlation between fasting PG and FLP (r2 = 0.06, P = .22). BMIz was also associated with FLP accuracy: FLP overestimated PG in children with low BMIz and underestimated PG in those with overweight/obesity for OGTT AUC and OGTT PG at baseline, 60, and 120 minutes (all P's ≤ .015). No adverse events occurred with FLP.ConclusionsAmong children without diabetes, the FLP was well tolerated and correlated with post-OGTT glucose, but had magnitude bias affecting fasting glucose and appeared to underestimate plasma glucose in those with overweight/obesity. These results suggest potential limitations for the utility of the FLP for research.
Project description:Continuous norming methods have seldom been subjected to scientific review. In this simulation study, we compared parametric with semi-parametric continuous norming methods in psychometric tests by constructing a fictitious population model within which a latent ability increases with age across seven age groups. We drew samples of different sizes (n = 50, 75, 100, 150, 250, 500 and 1,000 per age group) and simulated the results of an easy, medium, and difficult test scale based on Item Response Theory (IRT). We subjected the resulting data to different continuous norming methods and compared the data fit under the different test conditions with a representative cross-validation dataset of n = 10,000 per age group. The most significant differences were found in suboptimal (i.e., too easy or too difficult) test scales and in ability levels that were far from the population mean. We discuss the results with regard to the selection of the appropriate modeling techniques in psychometric test construction, the required sample sizes, and the requirement to report appropriate quantitative and qualitative test quality criteria for continuous norming methods in test manuals.
Project description:BackgroundAccurate determination of neutralization antibody titers supports epidemiological studies of dengue virus transmission and vaccine trials. Neutralization titers measured using the plaque reduction neutralization test (PRNT) are believed to provide a key measure of immunity to dengue viruses, however, the assay's variability is poorly understood, making it difficult to interpret the significance of any assay reading. In addition there is limited standardization of the neutralization evaluation point or statistical model used to estimate titers across laboratories, with little understanding of the optimum approach.Methodology/principal findingsWe used repeated assays on the same two pools of serum using five different viruses (2,319 assays) to characterize the variability in the technique under identical experimental conditions. We also assessed the performance of multiple statistical models to interpolate continuous values of neutralization titer from discrete measurements from serial dilutions. We found that the variance in plaque reductions for individual dilutions was 0.016, equivalent to a 95% confidence interval of 0.45-0.95 for an observed plaque reduction of 0.7. We identified PRNT75 as the optimum evaluation point with a variance of 0.025 (log10 scale), indicating a titer reading of 1∶500 had 95% confidence intervals of 1∶240-1∶1000 (2.70±0.31 on a log10 scale). The choice of statistical model was not important for the calculation of relative titers, however, cloglog regression out-performed alternatives where absolute titers are of interest. Finally, we estimated that only 0.7% of assays would falsely detect a four-fold difference in titers between acute and convalescent sera where no true difference exists.ConclusionsEstimating and reporting assay uncertainty will aid the interpretation of individual titers. Laboratories should perform a small number of repeat assays to generate their own variability estimates. These could be used to calculate confidence intervals for all reported titers and allow benchmarking of assay performance.
Project description:Hyperglycemia commonly occurs during surgery due to a reaction to metabolic stress and trauma. It has been shown that improper glycemia control leads to impaired wound healing and a higher risk of other postoperative complications.
The primary aim of our project is to assess the feasibility of the use of continuous glucose monitoring in measuring blood glucose levels in patients undergoing colorectal cancer surgery. The secondary aim is to analyze changes in perioperative blood glucose levels to understand the effects of stress and intraoperative interventions on the blood glucose level. The tertiary goal is to assess the predictive value of hyperglycemia for surgical site infection.
Project description:Osteosarcoma (OS) is the most common primary malignant bone tumor, which usually occurs in children and adolescents. It is generally a high-grade malignancy presenting with extreme metastases to the lungs or other bones. The etiology of the disease is multifaceted and still remains obscure. A combination of surgery and chemotherapy has played a major role in the treatment of OS over the past three decades, and consequently, the overall survival rates for the disease have remained unchanged. Therefore, there is an urgent need to employ new comprehensive analyses and technologies to develop significantly more informative classification systems, with the aim of developing more effective and less toxic therapies for OS patients. This review discusses the existing knowledge of OS therapy and potential methods to develop novel therapeutic agents for the disease.