Bright betatron x-ray radiation from a laser-driven-clustering gas target

Hard X-ray sources from femtosecond (fs) laser-produced plasmas, including the betatron X-rays from laser wakefield-accelerated electrons, have compact sizes, fs pulse duration and fs pump-probe capability, making it promising for wide use in material and biological sciences. Currently the main problem with such betatron X-ray sources is the limited average flux even with ultra-intense laser pulses. Here, we report ultra-bright betatron X-rays can be generated using a clustering gas jet target irradiated with a small size laser, where a ten-fold enhancement of the X-ray yield is achieved compared to the results obtained using a gas target. We suggest the increased X-ray photon is due to the existence of clusters in the gas, which results in increased total electron charge trapped for acceleration and larger wiggling amplitudes during the acceleration. This observation opens a route to produce high betatron average flux using small but high repetition rate laser facilities for applications

Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Comparison of Manual Cross-Sectional Measurements and Automatic Volumetry of the Corpus Callosum, and Their Clinical Impact: A Study on Type 1 Diabetes and Healthy Controls

Manually measured callosal area and automatically segmented are interchangeable. The association seen between callosal size with cerebral microbleeds and insulin resistance is indicative of small vessel disease pathology in diabetes type 1

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Progression to microalbuminuria in type 1 diabetes: development and validation of a prediction rule

AIMS/HYPOTHESIS: Microalbuminuria is common in type 1 diabetes and is associated with an increased risk of renal and cardiovascular disease. We aimed to develop and validate a clinical prediction rule that estimates the absolute risk of microalbuminuria. METHODS: Data from the European Diabetes Prospective Complications Study (n = 1115) were used to develop the prediction rule (development set). Multivariable logistic regression analysis was used to assess the association between potential predictors and progression to microalbuminuria within 7 years. The performance of the prediction rule was assessed with calibration and discrimination (concordance statistic [c-statistic]) measures. The rule was validated in three other diabetes studies (Pittsburgh Epidemiology of Diabetes Complications [EDC] study, Finnish Diabetic Nephropathy [FinnDiane] study and Coronary Artery Calcification in Type 1 Diabetes [CACTI] study). RESULTS: Of patients in the development set, 13% were microalbuminuric after 7 years. Glycosylated haemoglobin, AER, WHR, BMI and ever smoking were found to be the most important predictors. A high-risk group (n = 87 [8%]) was identified with a risk of progression to microalbuminuria of 32%. Predictions showed reasonable discriminative ability, with c-statistic of 0.71. The rule showed good calibration and discrimination in EDC, FinnDiane and CACTI (c-statistic 0.71, 0.79 and 0.79, respectively). CONCLUSIONS/INTERPRETATION: We developed and validated a clinical prediction rule that uses relatively easily obtainable patient characteristics to predict microalbuminuria in patients with type 1 diabetes. This rule can help clinicians to decide on more frequent check-ups for patients at high risk of microalbuminuria in order to prevent long-term chronic complication

Sphingomyelin is associated with kidney disease in type 1 diabetes (The FinnDiane Study)

Diabetic kidney disease, diagnosed by urinary albumin excretion rate (AER), is a critical symptom of chronic vascular injury in diabetes, and is associated with dyslipidemia and increased mortality. We investigated serum lipids in 326 subjects with type 1 diabetes: 56% of patients had normal AER, 17% had microalbuminuria (20 ≤ AER < 200 μg/min or 30 ≤ AER < 300 mg/24 h) and 26% had overt kidney disease (macroalbuminuria AER ≥ 200 μg/min or AER ≥ 300 mg/24 h). Lipoprotein subclass lipids and low-molecular-weight metabolites were quantified from native serum, and individual lipid species from the lipid extract of the native sample, using a proton NMR metabonomics platform. Sphingomyelin (odds ratio 2.53, P < 10−7), large VLDL cholesterol (odds ratio 2.36, P < 10−10), total triglycerides (odds ratio 1.88, P < 10−6), omega-9 and saturated fatty acids (odds ratio 1.82, P < 10−5), glucose disposal rate (odds ratio 0.44, P < 10−9), large HDL cholesterol (odds ratio 0.39, P < 10−9) and glomerular filtration rate (odds ratio 0.19, P < 10−10) were associated with kidney disease. No associations were found for polyunsaturated fatty acids or phospholipids. Sphingomyelin was a significant regressor of urinary albumin (P < 0.0001) in multivariate analysis with kidney function, glycemic control, body mass, blood pressure, triglycerides and HDL cholesterol. Kidney injury, sphingolipids and excess fatty acids have been linked in animal models—our exploratory approach provides independent support for this relationship in human patients with diabetes

Secretor Genotype (FUT2 gene) Is Strongly Associated with the Composition of Bifidobacteria in the Human Intestine

Intestinal microbiota plays an important role in human health, and its composition is determined by several factors, such as diet and host genotype. However, thus far it has remained unknown which host genes are determinants for the microbiota composition. We studied the diversity and abundance of dominant bacteria and bifidobacteria from the faecal samples of 71 healthy individuals. In this cohort, 14 were non-secretor individuals and the remainders were secretors. The secretor status is defined by the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucus and other secretions. It is determined by fucosyltransferase 2 enzyme, encoded by the FUT2 gene. Non-functional enzyme resulting from a nonsense mutation in the FUT2 gene leads to the non-secretor phenotype. PCR-DGGE and qPCR methods were applied for the intestinal microbiota analysis. Principal component analysis of bifidobacterial DGGE profiles showed that the samples of non-secretor individuals formed a separate cluster within the secretor samples. Moreover, bifidobacterial diversity (p<0.0001), richness (p<0.0003), and abundance (p<0.05) were significantly reduced in the samples from the non-secretor individuals as compared with those from the secretor individuals. The non-secretor individuals lacked, or were rarely colonized by, several genotypes related to B. bifidum, B. adolescentis and B. catenulatum/pseudocatenulatum. In contrast to bifidobacteria, several bacterial genotypes were more common and the richness (p<0.04) of dominant bacteria as detected by PCR-DGGE was higher in the non-secretor individuals than in the secretor individuals. We showed that the diversity and composition of the human bifidobacterial population is strongly associated with the histo-blood group ABH secretor/non-secretor status, which consequently appears to be one of the host genetic determinants for the composition of the intestinal microbiota. This association can be explained by the difference between the secretor and non-secretor individuals in their expression of ABH and Lewis glycan epitopes in the mucosa

Progression to microalbuminuria in patients with type 1 diabetes: a seven-year prospective study

<p>Abstract</p> <p>Background</p> <p>The presence of microalbuminuria can be associated with overt nephropathy and cardiovascular disease in patients with type 1 diabetes (T1D). We aimed to determine the incidence and evaluate the baseline predictors for the development of microalbuminuria in patients with T1D.</p> <p>Methods</p> <p>This study is a longitudinal cohort study of 122 normoalbuminuric patients with T1D who were receiving routine clinical care at baseline. A detailed medical history was taken, and a physical examination was performed at baseline. All of the patients were regularly examined for diabetes-associated complications. An analysis of predictors was performed using the Cox regression.</p> <p>Results</p> <p>Over 6.81 (3.59-9.75) years of follow-up, 50 (41%) of the patients developed microalbuminuria. The incidence density was 6.79/100 people per year (95% CI 5.04-8.95), and the microalbuminuria developed after 5.9 (2.44-7.76) and 11 (5-15) years of follow-up and diabetes duration, respectively. After an individual Cox regression, the baseline variables associated with the development of microalbuminuria were age, age at diagnosis, duration of diabetes, systolic and diastolic blood pressure, fasting glycemia, body mass index (BMI), total cholesterol and triglycerides levels, cholesterol/HDL ratio and a family history of type 2 diabetes.After a multivariate Cox regression, the only independent factors associated with the development of microalbuminuria were BMI [HR 1.12 (1.03-1.21)] and cholesterol/HDL ratio [HR 1.32 (1.05-1.67)].</p> <p>Conclusions</p> <p>A higher BMI and cholesterol/HDL ratio increased the risk of developing microalbuminuria in young patients with T1D after a short follow-up. Both risk factors are modifiable and should be identified early and followed closely.</p