Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and

A tunable plasma-based energy dechirper has been developed at FLASHForward to remove the correlated energy spread of a 681 MeV electron bunch. Through the interaction of the bunch with wakefields excited in plasma the projected energy spread was reduced from a FWHM of 1.31% to 0.33% without reducing the stability of the incoming beam. The experimental results for variable plasma density are in good agreement with analytic predictions and three-dimensional simulations. The proof-of-principle dechirping strength of 1.8  GeV/mm/m significantly exceeds those demonstrated for competing state-of-the-art techniques and may be key to future plasma wakefield-based free-electron lasers and high energy physics facilities, where large intrinsic chirps need to be removed.

Each successive generation of x-ray machines has opened up new frontiers in science, such as the first radiographs and the determination of the structure of DNA. State-of-the-art x-ray sources can now produce coherent high brightness keV x-rays and promise a new revolution in imaging complex systems on nanometre and femtosecond scales. Despite the demand, only a few dedicated synchrotron facilities exist worldwide, partially due the size and cost of conventional (accelerator) technology. Here we demonstrate the use of a recently developed compact laser-plasma accelerator to produce a well-collimated, spatially-coherent, intrinsically ultrafast source of hard x-rays. This method reduces the size of the synchrotron source from the tens of metres to centimetre scale, accelerating and wiggling a high electron charge simultaneously. This leads to a narrow-energy spread electron beam and x-ray source that is >1000 times brighter than previously reported plasma wiggler and thus has the potential to facilitate a myriad of uses across the whole spectrum of light-source applications.

Purpose

We examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus.

Materials and methods

Women enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model.

Results

A total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy.

Conclusions

The frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections.

We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.