Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques

We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6±1.0 years, BMI 31.5±0.4 kg/m2; 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6–62H2] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39–56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r2 = 27–32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations

The STAR Silicon Strip Detector (SSD)

The STAR Silicon Strip Detector (SSD) completes the three layers of the Silicon Vertex Tracker (SVT) to make an inner tracking system located inside the Time Projection Chamber (TPC). This additional fourth layer provides two dimensional hit position and energy loss measurements for charged particles, improving the extrapolation of TPC tracks through SVT hits. To match the high multiplicity of central Au+Au collisions at RHIC the double sided silicon strip technology was chosen which makes the SSD a half million channels detector. Dedicated electronics have been designed for both readout and control. Also a novel technique of bonding, the Tape Automated Bonding (TAB), was used to fullfill the large number of bounds to be done. All aspects of the SSD are shortly described here and test performances of produced detection modules as well as simulated results on hit reconstruction are given.Comment: 11 pages, 8 figures, 1 tabl

Online Monitoring of the Osiris Reactor with the Nucifer Neutrino Detector

Originally designed as a new nuclear reactor monitoring device, the Nucifer detector has successfully detected its first neutrinos. We provide the second shortest baseline measurement of the reactor neutrino flux. The detection of electron antineutrinos emitted in the decay chains of the fission products, combined with reactor core simulations, provides an new tool to assess both the thermal power and the fissile content of the whole nuclear core and could be used by the Inter- national Agency for Atomic Energy (IAEA) to enhance the Safeguards of civil nuclear reactors. Deployed at only 7.2m away from the compact Osiris research reactor core (70MW) operating at the Saclay research centre of the French Alternative Energies and Atomic Energy Commission (CEA), the experiment also exhibits a well-suited configuration to search for a new short baseline oscillation. We report the first results of the Nucifer experiment, describing the performances of the 0.85m3 detector remotely operating at a shallow depth equivalent to 12m of water and under intense background radiation conditions. Based on 145 (106) days of data with reactor ON (OFF), leading to the detection of an estimated 40760 electron antineutrinos, the mean number of detected antineutrinos is 281 +- 7(stat) +- 18(syst) electron antineutrinos/day, in agreement with the prediction 277(23) electron antineutrinos/day. Due the the large background no conclusive results on the existence of light sterile neutrinos could be derived, however. As a first societal application we quantify how antineutrinos could be used for the Plutonium Management and Disposition Agreement.Comment: 22 pages, 16 figures - Version

Invest Ophthalmol Vis Sci

Purpose: To analyze the association between skin autofluorescence (sAF), estimating tissue accumulation of advanced glycation end-products (AGEs), and open angle glaucoma (OAG) in an elderly population. Methods: The Antioxydants, Lipides Essentiels, Nutrition and maladies OculaiRes (ALIENOR) study is an on-going epidemiologic population-based study on age-related eye diseases. In 2009 to 2010, 624 subjects, aged 74 years or older, were recruited. All subjects underwent a complete eye examination, including optic disc color photography and spectral-domain optical coherence tomography (SD-OCT) examination. Sociodemographic and medical history data were collected using standardized questionnaires. Glaucoma diagnosis was made using optic nerve head retinophotography and International Society for Epidemiologic and Geographical Ophthalmology criteria. sAF was measured with a noninvasive autofluorescence reader in 467 subjects. Results: Of subjects, 455 had complete data, 424 were classified as controls, and 31 classified as OAG. Mean age was 82.3 +/- 4.3 years, mean and median sAF were 2.8 +/- 0.7 and 2.7 arbitrary units (AU), respectively. In a multivariate analysis, higher sAF values (>/=2.7 AU) were associated with OAG (odds ratio [OR] = 2.28, 95% Confidence Interval [CI]: 1.03; 5.04). Other variables significantly associated with OAG were age (OR = 1.10, 95%CI: 1.00; 1.21), glaucoma family history (OR = 2.83, 95%CI: 1.14; 7.01) and smoking (1-20 pack-years [OR = 3.31, 95%CI: 1.18; 9.26]; >/=20 pack-years [OR = 3.85, 95%CI: 1.42; 10.46]). Conclusions: Higher level of sAF, which may act as a long-term biomarker of metabolic memory, and smoking are independently associated with an increased risk of glaucoma. Long-term accumulation of AGEs, a marker of oxidative stress, could play a role in the pathogenesis of glaucomatous chronic optic neuropathy

Periodontal treatment to improve glycaemic control in diabetic patients: study protocol of the randomized, controlled DIAPERIO trial

<p>Abstract</p> <p>Background</p> <p>Periodontitis is a common, chronic inflammatory disease caused by gram-negative bacteria leading to destruction of tissues supporting the teeth. Epidemiological studies have consistently shown increased frequency, extent and severity of periodontitis among diabetic adults. More recently, some controlled clinical trials have also suggested that periodontal treatment could improve glycaemic control in diabetic patients. However current evidence does not provide sufficient information on which to confidently base any clinical recommendations. The main objective of this clinical trial is to assess whether periodontal treatment could lead to a decrease in glycated haemoglobin levels in metabolically unbalanced diabetic patients suffering from chronic periodontitis.</p> <p>Methods</p> <p>The DIAPERIO trial is an open-label, 13-week follow-up, randomized, controlled trial. The total target sample size is planned at 150 participants, with a balanced (1:1) treatment allocation (immediate treatment vs delayed treatment). Periodontal treatment will include full mouth non-surgical scaling and root planing, systemic antibiotherapy, local antiseptics (chlorhexidine 0.12%) and oral health instructions. The primary outcome will be the difference in change of HbA1c between the two groups after the 13-weeks' follow-up. Secondary outcomes will be the difference in change of fructosamine levels and quality of life between the two groups.</p> <p>Discussion</p> <p>The DIAPERIO trial will provide insight into the question of whether periodontal treatment could lead to an improvement in glycaemic control in metabolically unbalanced diabetic patients suffering from periodontitis. The results of this trial will help to provide evidence-based recommendations for clinicians and a draft framework for designing national health policies.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN15334496</p

Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area

Background: Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM). Methods: Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke). Variables of renal function were defined as follows: 1) Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2) Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3) Kidney disease (KD): glomerular filtration rate according to Modification of Diet in Renal Disease < 60 ml/min/1.73 m2 and/or the presence of albuminuria, 4) Renal impairment (RI): glomerular filtration rate < 60 ml/min/1.73 m2, 5) Nonalbuminuric RI: glomerular filtration rate < 60 ml/min/1.73 m2 without albuminuria and, 5) Diabetic nephropathy (DN): macroalbuminuria or microalbuminuria plus diabetic retinopathy. Results: The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN). The prevalence of albuminuria without RI (13.5%) and nonalbuminuric RI (14.7%) was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86-2.59), microvascular disease (OR 2.14; CI 95% 1.8-2.54) and insulin treatment (OR 1.82; CI 95% 1.39-2.38), and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80-0.91). Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21-0.35), duration of diabetes (OR 0.94 per year; CI 95% 0.91-0.97) and directly associated with HbA1c (OR 1.19 for every 1% increase; CI 95% 1.09-1.3). Conclusions: One-third of the sample population in this study has KD. The presence or absence of albuminuria identifies two subgroups with different characteristics related to gender, the duration of diabetes and metabolic status of the patient. It is important to determine both albuminuria and GFR estimation to diagnose KD

Cardiovasc Diabetol

BACKGROUND: Advanced glycation end-products play a role in diabetic vascular complications. Their optical properties allow to estimate their accumulation in tissues by measuring the skin autofluorescence (SAF). We searched for an association between SAF and major adverse cardiovascular events (MACE) incidence in subjects with Type 1 Diabetes (T1D) during a 7 year follow-up. METHODS: During year 2009, 232 subjects with T1D were included. SAF measurement, clinical [age, sex, body mass index (BMI), comorbidities] and biological data (HbA1C, blood lipids, renal parameters) were recorded. MACE (myocardial infarction, stroke, lower extremity amputation or a revascularization procedure) were registered at visits in the center or by phone call to general practitioners until 2016. RESULTS: The participants were mainly men (59.5%), 51.5 +/- 16.7 years old, with BMI 25.0 +/- 4.1 kg/m(2), diabetes duration 21.5 +/- 13.6 years, HbA1C 7.6 +/- 1.1%. LDL cholesterol was 1.04 +/- 0.29 g/L, estimated Glomerular Filtration Rates (CKD-EPI): 86.3 +/- 26.6 ml/min/1.73 m(2). Among these subjects, 25.1% were smokers, 45.3% had arterial hypertension, 15.9% had elevated AER (>/= 30 mg/24 h), and 9.9% subjects had a history of previous MACE. From 2009 to 2016, 22 patients had at least one new MACE: 6 myocardial infarctions, 1 lower limb amputation, 15 revascularization procedures. Their SAF was 2.63 +/- 0.73 arbitrary units (AU) vs 2.08 +/- 0.54 for other patients (p = 0.002). Using Cox-model, after adjustment for age (as the scale time), sex, diabetes duration, BMI, hypertension, smoking status, albumin excretion rates, statin treatment and a previous history of MACE, higher baseline levels of SAF were significantly associated with an increased risk of MACE during follow-up (HR = 4.13 [1.30-13.07]; p = 0.02 for 1 AU of SAF) and Kaplan-Meier curve follow-up showed significantly more frequent MACE in group with SAF upper the median (p = 0.001). CONCLUSION: A high SAF predicts MACE in patients with T1D

The Control Unit of the KM3NeT Data Acquisition System

The KM3NeT Collaboration runs a multi-site neutrino observatory in the Mediterranean Sea. Water Cherenkov particle detectors, deep in the sea and far off the coasts of France and Italy, are already taking data while incremental construction progresses. Data Acquisition Control software is operating off-shore detectors as well as testing and qualification stations for their components. The software, named Control Unit, is highly modular. It can undergo upgrades and reconfiguration with the acquisition running. Interplay with the central database of the Collaboration is obtained in a way that allows for data taking even if Internet links fail. In order to simplify the management of computing resources in the long term, and to cope with possible hardware failures of one or more computers, the KM3NeT Control Unit software features a custom dynamic resource provisioning and failover technology, which is especially important for ensuring continuity in case of rare transient events in multi-messenger astronomy. The software architecture relies on ubiquitous tools and broadly adopted technologies and has been successfully tested on several operating systems

Dependence of atmospheric muon flux on seawater depth measured with the first KM3NeT detection units: The KM3NeT Collaboration

KM3NeT is a research infrastructure located in the Mediterranean Sea, that will consist of two deep-sea Cherenkov neutrino detectors. With one detector (ARCA), the KM3NeT Collaboration aims at identifying and studying TeV–PeV astrophysical neutrino sources. With the other detector (ORCA), the neutrino mass ordering will be determined by studying GeV-scale atmospheric neutrino oscillations. The first KM3NeT detection units were deployed at the Italian and French sites between 2015 and 2017. In this paper, a description of the detector is presented, together with a summary of the procedures used to calibrate the detector in-situ. Finally, the measurement of the atmospheric muon flux between 2232–3386 m seawater depth is obtained

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms